Neuronal cell death in human neurodegenerative diseases and their animal/cell models

doi:10.1017/CBO9780511663543.005

4 - Neuronal cell death in human neurodegenerative diseases and their animal/cell models

Published online by Cambridge University Press: 03 March 2010

Juan Troncoso and

Edited by

Alex E. MacKenzie and

Robert G. Korneluk

Show author details

Lee J. Martin: Affiliation:
Departments of Pathology, Division of Neuropathology, Neuroscience, and Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Zhiping Liu: Affiliation:
Departments of Pathology, Division of Neuropathology, Neuroscience, and Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Juan Troncoso: Affiliation:
Departments of Pathology, Division of Neuropathology, Neuroscience, and Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Donald L. Price: Affiliation:
Departments of Pathology, Division of Neuropathology, Neuroscience, and Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Martin Holcik: Affiliation:
University of Ottawa
Eric C. LaCasse: Affiliation:
University of Ottawa
Alex E. MacKenzie: Affiliation:
University of Ottawa
Robert G. Korneluk: Affiliation:
University of Ottawa

Book contents

Get access

Summary

Introduction

Cell death is important in the normal histogenesis of organs, steady state kinetics of healthy adult tissues, pathogenesis of tissue damage and disease, and disease therapy. Pathologists conceived the concept of cell death as a mechanism for disease to aid in diagnosis and therapy (Virchow, 1858). Developmental biologists then realized the essential role of cell death in tissue and organ development (Glücksmann, 1951; Lockshin and Williams, 1964; Saunders, 1966). This idea was at first received with skepticism, but now it is dogma that cell number in tissues is controlled precisely in developing and adult tissues. The absence of this precise control of cell number in tissues causes cancer (impaired apoptosis is a central step toward neoplasia). Pathologic stimuli can be extrinsic or intrinsic and can inactivate normal cell death networks or can cause abrupt or delayed cell death. Cell demise can occur as multiple types of death (Schweichel and Merker, 1973; Lockshin and Zakeri, 2002). It is compelling that a goal of human disease therapy is, on the one hand, to prevent cell death in neurologic disease and, on the other hand, to stimulate cell death in malignancy. Thus, the study of cell death is fundamental to human pathobiology and disease treatment. In this chapter, recent critical views on the contributions of the different forms of cell death to human neurodegenerative diseases and their animal and cell models will be presented.

Information

Type: Chapter
Information: Apoptosis in Health and Disease
Clinical and Therapeutic Aspects
, pp. 96 - 155

DOI: https://doi.org/10.1017/CBO9780511663543.005 [Opens in a new window]

Publisher: Cambridge University Press

Print publication year: 2005

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Book purchase

Temporarily unavailable

References

Adamec, E., Vonsattel, J. P., and Nixon, R. A. (1999). DNA strand breaks in Alzheimer's disease. Brain Res., 849, 67–77CrossRef Google Scholar PubMed

Al-Abdulla, N. A. and Martin, L. J. (1998). Apoptosis of retrogradely degenerating neurons occurs in association with the accumulation of perikaryal mitochondria and oxidative damage to the nucleus. Am. J. Pathol., 153, 447–56CrossRef Google Scholar PubMed

Al-Abdulla, N. A., Portera-Cailliau, C., and Martin, L. J. (1998). Occipital cortex ablation in adult rat causes retrograde neuronal death in the lateral geniculate nucleus that resembles apoptosis. Neuroscience, 86, 191–209CrossRef Google Scholar PubMed

Aloyz, R. S., Bamji, S. X., Pozniak, C. D.et al. (1998). p53 is essential for developmental neuron death regulated by the TrkA and p75 neurotrophin receptors. J. Cell Biol., 143, 1691–703CrossRef Google Scholar PubMed

Alvarez, A., Munoz, J. P., and Maccioni, R. B. (2001). A cdk5-p35 stable complex is involved in the β-amyloid-induced deregulation of cdk5 activity in hippocampal neurons. Exp. Cell Res., 264, 266–74CrossRef Google Scholar PubMed

Alves da Costa, C., Paitel, E., Vincent, B., and Checler, F. (2002). Alpha-synuclein lowers p53-dependent apoptotic of neuronal cell: abolishment by 6-hydroxydopamine and implication for Parkinson's disease. J. Biol. Chem., 277, 50980–4CrossRef Google Scholar PubMed

Ameisen, J. C. (2002). On the origin, evolution, and nature of programmed cell death: a timeline of four billion years. Cell Death Diff., 9, 367–93CrossRef Google Scholar PubMed

Amin, F., Bowen, I. D., Szegedi, Z., Mihalik, R., and Szende, B. (2000). Apoptotic and non-apoptotic modes of programmed cell death in MCF-7 human breast carcinoma cells. Cell Biol. Intl., 24, 253–60CrossRef Google Scholar PubMed

Anderson, A. J., Su, J. H., and Cotman, C. W. (1996). DNA damage and apoptosis in Alzheimer's disease: colocalization with c-jun immunoreactivity, relationship to brain area, and effect of postmortem delay. J. Neurosci., 16, 1710–19CrossRef Google Scholar PubMed

Anglade, P., Vyas, S., Javoy-Agid, F.et al. (1997). Apoptosis and autophagy in nigral neurons of patients with Parkinson's disease. Histol. Histopathol., 12, 25–31Google Scholar PubMed

Ankarcrona, M., Dypbukt, J. M., Bonfoco, E.et al. (1995). Glutamate-induced neuronal death: a succession of necrosis or apoptosis depending on mitochondrial function. Neuron, 15, 961–73CrossRef Google Scholar PubMed

Antonsson, B., Conti, F., Ciavatta, A.et al. (1997). Inhibition of bax channel-forming activity by bcl-2. Science, 277, 370–2CrossRef Google Scholar PubMed

Barron, K. D., Means, E. D., and Larsen, E . (1973). Ultrastructure of retrograde degeneration in thalamus of rat. I. Neuronal somata and dendrites. J. Neuropathol. Exp. Neurol., 32, 218–44CrossRef Google Scholar PubMed

Beckman, J. S., Carson, M., Smith, C. D., and Koppenol, W. H. (1993). ALS, SOD and peroxynitrite. Nature, 364, 548CrossRef Google Scholar PubMed

Beckman, J. S., Estōvez, A. G., Crow, J. P., and Barbeito, , L. (2001). Superoxide dismutase and the death of motoneurons in ALS. Trends Neurosci., 24 (suppl), S15–S20CrossRef Google Scholar PubMed

Behl, C., Davis, J. B., Klier, F. G., and Schubert, D. (1994). Amyloid beta peptide induces necrosis rather than apoptosis. Brain Res., 645, 253–64CrossRef Google Scholar PubMed

Bendotti, C., Calvaresi, N., Chiveri, L.et al. (2001). Early vacuolization and mitochondrial damage in motor neurons of FALS mice are not associated with apoptosis or with changes in cytochrome oxidase histochemical reactivity. J. Neurol. Sci., 191, 25–33CrossRef Google Scholar PubMed

Beresford, P. J., Zhang, D., Oh, D. Y.et al. (2001). Granzyme A activates an endoplasmic reticulum-associated caspase-independent nuclease to induce single-stranded DNA nicks. J. Biol. Chem., 276, 43285–93CrossRef Google Scholar PubMed

Bilsland, J., Roy, S., Xanthoudakis, S.et al. (2002). Caspase inhibitors attenuate 1-methyl-4-phenylpyridinum toxicity in primary cultures of mesencephalic dopaminergic neurons. J. Neurosci., 22, 2637–49CrossRef Google Scholar

Blum, D., Wu, Y., Nissou, M-F., Arnaud, S., Benabid, A.-L., and Verna, J.-M. (1997). p53 and Bax activation in 6-hydroxydopamine-induced apoptosis in PC12 cells. Brain Res., 751, 139–42CrossRef Google Scholar PubMed

Bonfanti, L., Strettoi, E., Chierzi, S.et al. (1996). Protection of retinal ganglion cells from natural and axotomy-induced cell death in neonatal transgenic mice overexpressing bcl-2. J. Neurosci., 16, 4186–94CrossRef Google Scholar PubMed

Bonfoco, E., Krainc, D., Ankarcrona, M., Nicotera, P., and Lipton, S. A. (1995). Apoptosis and necrosis: two distinct events induced, respectively, by mild and intense insults with N-methyl-D-aspartate or nitric oxide/superoxide in cortical cell culture. Proc. Natl. Acad. Sci. USA, 92, 7162–6CrossRef Google Scholar PubMed

Bradley, W. G. and Krasin, F. (1982). A new hypothesis of the etiology of amyotrophic lateral sclerosis. The DNA hypothesis. Arch. Neurol., 39, 677–80CrossRef Google Scholar PubMed

Bucciantini, M., Giannoni, E., Chiti, F.et al. (2002). Inherent toxicity of aggregates implies a common mechanism for misfolding diseases. Nature, 416, 507–11CrossRef Google Scholar PubMed

Bursch, W. (2001). The autophagosomal-lysosomal compartment in programmed cell death. Cell Death Diff., 8, 569–81CrossRef Google Scholar PubMed

Bursch, W., Paffe, S., Putz, B., Barthel, G., and Schulte-Hermann, R. (1990). Determination of the length of the histological stages of apoptosis in normal liver and in altered hepatic foci of rats. Carcinogenesis, 11, 847–53CrossRef Google Scholar PubMed

Bursztajn, S., DeSouza, R., McPhie, D. L.et al. (1998). Overexpression in neurons of human presenilin-1 or a presenilin-1 familial Alzheimer disease mutant does not enhance apoptosis. J. Neurosci., 18, 9790–9CrossRef Google Scholar

Calhoun, M. E., Wiederhold, K. H., Abramowski, D.et al. (1998). Neuron loss in APP transgenic mice. Nature, 395, 755–6CrossRef Google Scholar PubMed

Campion, D., Flaman, J. M., Brice, A.et al. (1995). Mutations of the presenilin 1 gene in families with early-onset Alzheimer's disease. Hum. Mol. Genet., 4, 2373–7CrossRef Google Scholar PubMed

Cardone, M. H., Roy, N., Stennicke, H. R.et al. (1998). Regulation of cell death protease caspase-9 by phosphorylation. Science, 282, 1318–21CrossRef Google Scholar PubMed

Cardone, M. H., Salvesen, G. S., Widmann, C., Johnson, G., and Frisch, S. M. (1997). The regulation of anoikis: MEKK-1 activation requires cleavage by caspases. Cell, 90, 315–23CrossRef Google Scholar PubMed

Casaccia-Bonnefil, P., Carter, B. D., Dobrowsky, R. T., and Chao, M. V. (1996). Death of oligodendrocytes mediated by the interaction of nerve growth factor with its receptor p75. Nature, 383, 716–19CrossRef Google Scholar PubMed

Casley, C. S., Land, J. M., Sharpe, M. A., Clark, J. B., Duchen, M. R., and Canevari, L. (2002). β-amyloid fragment 25–35 causes mitochondrial dysfunction in primary cortical neurons. Neurobiol. Dis., 10, 258–67CrossRef Google Scholar PubMed

Cataldo, A. M., Hamilton, D. J., and Nixon, R. A. (1994). Lysosomal abnormalities in degenerating neurons link neuronal compromise to senile plaque development in Alzheimer's disease. Brain Res., 640, 68–80CrossRef Google Scholar

Chan, S. L., Culmsee, C., Haughey, N., Klapper, W., and Mattson, M. P. (2002). Presenilin-1 mutations sensitize neurons to DNA damage-induced death by a mechanism involving perturbed calcium homeostasis and activation of calpains and caspase-12. Neurobiol. Dis., 11, 2–19CrossRef Google Scholar PubMed

Chang, Y.-C., Lee, Y.-S., Tejima, T.et al. (1998). Mdm-2 and bax, downstream mediators of the p53 response, are degraded by the ubiquitin-proteasome pathway. Cell Growth Diff., 9, 79–84Google Scholar

Chartier-Harlin, M.-C., Crawford, F., Houlden, H.et al. (1991). Early-onset Alzheimer's disease caused by mutations at codon 717 of the β-amyloid precursor protein gene. Nature, 353, 844–6CrossRef Google Scholar PubMed

Choi, D. W. (1992). Excitotoxic cell death. J. Neurobiol., 23, 1261–76CrossRef Google Scholar PubMed

Chu-Wang, I.-W. and Oppenheim, R. W. (1978). Cell death of motoneurons in the chick embryo spinal cord. I. A light and electron microscopic study of naturally occurring and induced cell loss during development. J. Comp. Neurol., 177, 33–58CrossRef Google Scholar PubMed

Clarke, P. G. H. (1990). Developmental cell death: morphological diversity and multiple mechanisms. Anat. Embryol., 181, 195–213CrossRef Google Scholar PubMed

Cory, S. and Adams, J. M. (2002). The bcl-2 family: regulators of the cellular life-or-death switch. Nat. Rev., 2, 647–56CrossRef Google Scholar PubMed

Crocker, S. J., Wigle, N., Liston, P.et al. (2001). NAIP protects the nigrostriatal dopamine pathway in an intrastriatal 6-OHDA rat model of Parkinson's disease. Eur. J. Neurosci., 14, 391–400CrossRef Google Scholar

Crompton, M. (1999). The mitochondrial permeability transition pore and its role in cell death. Biochem. J., 341, 233–49CrossRef Google Scholar PubMed

Cruz, J. C., Tseng, H. C., Goldman, J. A., Shih, H., and Tsai, L.-H. (2003). Aberrant Cdk5 activation by p25 triggers pathological events leading to neurodegeneration and neurofibrillary tangles. Neuron, 40, 471–83CrossRef Google Scholar PubMed

Culmsee, C., Zhu, X., Yu, Q. S.et al. (2001). A synthetic inhibitor of p53 protects neurons against death induced by ischemic and excitotoxic insults, and amyloid beta-peptide. J. Neurochem., 77, 220–8CrossRef Google Scholar PubMed

Danial, N. N., Gramm, C. F., Scorrano, L.et al. (2003). Bad and glucokinase reside in a mitochondrial complex that integrates glycolysis and apoptosis. Nature, 424, 952–6CrossRef Google Scholar

Dargusch, R., Piasecki, D., Tan, S., Liu, Y., and Schubert, D. (2001). The role of Bax in glutamate-induced nerve cell death. J. Neurochem., 76, 295–301CrossRef Google Scholar PubMed

Datta, S. R., Dudek, H., Tao, X.et al. (1997). Akt phosphorylation of Bad couples survival signals to the cell-intrinsic death machinery. Cell, 91, 231–41CrossRef Google Scholar PubMed

Davies, S. W., Turmaine, M., Cozens, B. A.et al. (1997). Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation. Cell, 90, 537–48CrossRef Google Scholar PubMed

Aguilar, J. L. G., Gorden, J. W., Rene, F.et al. (2000). Alteration of the cl-x/Bax ratio in a transgenic mouse model of amyotrophic lateral sclerosis: evidence for the implication of the p53 signaling pathway. Neurobiol. Dis., 7, 406–15CrossRef Google Scholar

Deak, J. C., Cross, J. V., Lewis, M.et al. (1998). Fas-induced proteolytic activation and intracellular redistribution of the stress-signaling kinase MEKK1. Proc. Natl. Acad. Sci. USA, 95, 5595–600CrossRef Google Scholar PubMed

Deckwerth, T. L., Elliott, J. L., Knudson, C. M., Johnson, E. M., Snider, W. D., and Korsmeyer, S. J. (1996). Bax is required for neuronal death after trophic factor deprivation and during development. Neuron, 17, 401–11CrossRef Google Scholar PubMed

DeKosky, S. T. and Scheff, S. W. (1990). Synapse loss in frontal cortex biopsies in Alzheimer's disease: correlation with cognitive severity. Ann. Neurol., 27, 457–64CrossRef Google Scholar PubMed

Monte, S., Sohn, Y. K., and Wands, J. R. (1997). Correlates of p53- and Fas (CD95)-mediated apoptosis in Alzheimer's disease. J. Neurol. Sci., 152, 73–83CrossRef Google Scholar PubMed

Monte, S. M., Sohn, Y. K., Ganju, N., and Wands, J. R. (1998). p53- and CD95-associated apoptosis in neurodegenerative diseases. Lab. Invest., 78, 401–11Google Scholar PubMed

del Peso, L., Gonzlez-Garcia, M., Page, C., Herrera, R., and Nuez, G. (1997). Interleukin-3-induced phosphorylation of bad through the protein kinase Akt. Science, 278, 687–9CrossRef Google Scholar PubMed

Deng, H.-X., Hentati, A., Tainer, J. A.et al. (1993). Amyotrophic lateral sclerosis and structural defects in Cu, Zn superoxide dismutase. Science, 261, 1047–51CrossRef Google Scholar PubMed

Desagher, S., Osen-Sand, A., Nichols, A.et al. (1999). Bid-induced conformational change of bax is responsible for mitochondrial cytochrome c release during apoptosis. J. Cell Biol., 144, 891–901CrossRef Google Scholar PubMed

Dessi, F., Charriaut-Marlangue, C., Khrestchatisky, M., and Ben-Ari, Y. (1993). Glutamate-induced neuronal death is not a programmed cell death in cerebellar culture. J. Neurochem., 60, 1953–5CrossRef Google Scholar

Deveraux, Q. L., Roy, N., Stennicke, H. R.et al. (1998). IAPs block apoptotic events induced by caspase-8 and cytochrome c by direct inhibition of distinct caspases. EMBO J., 17, 2215–23CrossRef Google Scholar PubMed

Di Cristofano, A., Pesce, B., Cordon-Cardo, C., and Pandolfi, P. P. (1998). Pten is essential for embryonic development and tumor suppression. Nat. Genet., 19, 348–55CrossRef Google Scholar

Du, C., Fang, M., Li, Y., Li, L., and Wang, X. (2000). Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition. Cell, 102, 33–42CrossRef Google Scholar PubMed

Dubois-Dauphin, M., Frankowski, H., Tsujimoto, Y., Huarte, J., and Martinou, J.-C. (1994). Neonatal motoneurons overexpressing the bcl-2 protooncogene in transgenic mice are protected from axotomy-induced cell death. Proc. Natl. Acad. Sci. USA, 91, 3309–13CrossRef Google Scholar PubMed

Duker, N. J., Sperling, J., Soprano, K. J., Druin, D. P., Davis, A., and Ashworth, R. (2001). β-amyloid protein induces the formation of purine dimers in cellular DNA. J. Cell Biochem., 81, 393–4003.0.CO;2-5>CrossRef Google Scholar PubMed

English, J., Pearson, G., Wilsbacher, J.et al. (1999). New insights into the control of MAP kinase pathways. Exp. Cell Res., 253, 255–70CrossRef Google Scholar PubMed

Ethell, D. W., Kinloch, R., and Green, D. R. (2002). Metalloproteinase shedding of Fas ligand regulates beta-amyloid neurotoxicity. Curr. Biol., 12, 1595–600CrossRef Google Scholar PubMed

Evans, D. A., Funkenstein, H. H., Albert, M. S.et al. (1989). Prevalence of Alzheimer's disease in a community population of older persons: higher than previously reported. JAMA, 262, 2551–6CrossRef Google Scholar

Fan, Z., Beresford, P. J., Oh, D. Y., Zhang, D., and Lieberman, J. (2003). Tumor suppressor NM23-H1 is a granzyme A-activated DNase during TL-mediated apoptosis, and the nucleosome assembly protein SET is its inhibitor. Cell, 112, 659–72CrossRef Google Scholar

Farlie, P. G., Dringen, R., Rees, S. M., Kannourakis, G., and Bernard, O. (1995). Bcl-2 transgene expression can protect neurons against developmental and induced cell death. Proc. Natl. Acad. Sci. USA, 92, 4397–401CrossRef Google Scholar PubMed

Fath, T., Eidenmuller, J., and Brandt, R. (2002). Tau-mediated cytotoxicity in a pseudohyperphosphorylation model of Alzheimer's disease. J. Neurosci., 22, 9733–41CrossRef Google Scholar

Fernandes, R. S. and Cotter, T. G. (1994). Apoptosis or necrosis: intracellular levels of glutathione influence mode of cell death. Biochem. Pharmacol., 48, 675–81CrossRef Google Scholar PubMed

Ferrante, R. J., Browne, S. E., Shinobu, L. A.et al. (1997). Evidence of increased oxidative damage in both sporadic and familial amyotrophic lateral sclerosis. J. Neurochem., 69, 2064–74CrossRef Google Scholar PubMed

Ferrer, I., Puig, B., Krupinski, J., Carmona, M., and Blanco, R. (2001). Fas and Fas ligand expression in Alzheimer's disease. Acta. Neuropathol., 102, 121–31Google Scholar PubMed

Fitzmaurice, P. S., Shaw, I. C., Kleiner, H. E.et al. (1996). Evidence for DNA damage in amyotrophic lateral sclerosis. Muscle. Nerve., 19, 797–8Google Scholar PubMed

Friedlander, R. M., Brown, R. H., Gagliardini, V., Wang, J., and Yuan, J. (1997). Inhibition of ICE slows ALS in mice. Nature, 388, 31CrossRef Google Scholar PubMed

Froelich, S., Basun, H., Forsell, C.et al. (1997). Mapping of a disease locus for familial rapidly progressive frontotemporal dementia to chromosome 17q12–21. Am. J. Med. Genet., 74, 380–53.0.CO;2-T>CrossRef Google Scholar PubMed

Gamliel, A., Teicher, C., Hartmann, T., Beyreuther, K., and Stein, R. (2003). Overexpression of wild-type presenilin 2 or its familial Alzheimer's disease-associated mutant does not induce or increase susceptibility to apoptosis in different cells. Neuroscience, 117, 119–28CrossRef Google Scholar

Gastard, M. C., Troncoso, J. C., and Koliatsos, V. E. (2003). Caspase activation in the limbic cortex of subjects with early Alzheimer's disease. Ann. Neurol., 54, 393–8CrossRef Google Scholar PubMed

Gervais, F. G., Singaraja, R., Xanthoudakis, S.et al. (2002). Recruitment and activation of caspase-8 by the Huntingtin-interacting protein Hip-1 and a novel partner Hippi. Nat. Cell Biol., 4, 95–105CrossRef Google Scholar

Gervais, F. G., Xu, D., Robertson, G. S.et al. (1999). Involvement of caspases in proteolytic cleavage of Alzheimer's amyloid-beta precursor protein and amyloidogenic A beta peptide formation. Cell, 97, 395–406CrossRef Google Scholar PubMed

Giaccia, A. J. and Kastan, M. B. (1998). The complexity of p53 modulation: emerging patterns from divergent signals. Genes Develop., 12, 2973–83CrossRef Google Scholar PubMed

Giasson, B. I., Duda, J. E., Murray, I. V. J.et al. (2000). Oxidative damage linked to neurodegeneration by selective alpha-synuclein nitration in synucleinopathy lesions. Science, 290, 985–9CrossRef Google Scholar PubMed

Gilman, C. P., Chan, S. L., Guo, Z., Zhu, X., Greig, N., and Mattson, M. P. (2003). p53 is present in synapses where it mediates mitochondrial dysfunction and synaptic degeneration in response to DNA damage, and oxidative and excitotoxic insults. Neuromolecular Med., 3, 159–72CrossRef Google Scholar PubMed

Giovanni, A., Keramaris, E., Morris, E. J.et al. (2000). E2F1 mediates death of β-amyloid-treated cortical neurons in a manner independent of p53 and dependent on Bax and caspase 3. J. Biol. Chem., 275, 11553–60CrossRef Google Scholar

Glücksmann, A. (1951). Cell deaths in normal vertebrate ontogeny. Biol. Rev., 26, 59–86CrossRef Google Scholar PubMed

Goate, A., Chartier-Harlin, M.-C., Mullan, M.et al. (1991). Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature, 349, 704–6CrossRef Google Scholar PubMed

Golden, W. C., Brambrink, A. M., Traystman, R. J., and Martin, L. J. (2001). Failure to sustain recovery of Na, K ATPase function is a possible mechanism for striatal neurodegeneration in hypoxic-ischemic newborn piglets. Mol. Brain Res., 88, 94–102CrossRef Google Scholar PubMed

Goldschmidt, R. B. and Steward, O. (1980). Preferential neurotoxicity of colchicine for granule cells of the dentate gyrus of adult rat. Proc. Natl. Acad. Sci. USA, 77, 3047–51CrossRef Google Scholar PubMed

Gotz, J., Chen, F., Barmettler, R., and Nitsch, R. M. (2001a). Tau filament formation in transgenic mice expressing P301L tau. J. Biol. Chem., 276, 529–34CrossRef Google Scholar

Gotz, J., Chen, F., Dorpe, J., and Nitsch, R. M. (2001b). Formation of neurofibrillary tangles in P301l tau transgenic mice induced by Abeta 42 fibrils. Science, 293, 1491–5CrossRef Google Scholar

Gomez-Isla, T., Price, J. L., McKeel, D. W. Jr.., Growdon, J. H., and Hyman, B. T. (1996). Profound loss of layer II entorhinal cortex neurons occurs in very mild Alzheimer's disease. J. Neurosci., 16, 4491–500CrossRef Google Scholar PubMed

Guegan, C., Vila, M., Rosoklija, G., Hays, A. P., and Przeborski, S. (2001). Recruitment of the mitochondrial-dependent apoptotic pathway in amyotrophic lateral sclerosis. J. Neurosci., 21, 6569–76CrossRef Google Scholar PubMed

Gwag, B. J., Koh, J. Y., DeMaro, J. A., Ying, H. S., Jacquin, M., and Choi, D. W. (1997). Slowly triggered excitotoxicity occurs by necrosis in cortical cultures. Neuroscience, 77, 393–401CrossRef Google Scholar PubMed

Hackam, A. S., Yassa, A. S., Singaraja, R.et al. (2000). Huntingtin interacting protein 1 induces apoptosis via a novel caspase-dependent death effector domain. J. Biol. Chem., 275, 41299–308CrossRef Google Scholar

Hakem, R., Hakem, A., Duncan, G. S.et al. (1998). Differential requirement for caspase 9 in apoptotic pathways in vivo. Cell, 94, 339–52CrossRef Google Scholar PubMed

Haldar, S., Jena, N., and Croce, C. M. (1995). Inactivation of Bcl-2 by phosphorylation. Proc. Natl. Acad. Sci. USA, 92, 4507–11CrossRef Google Scholar PubMed

Hardy, J. and Selkoe, D. J. (2002). The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science, 297, 353–6CrossRef Google Scholar PubMed

Harper, P. S. (1996). Huntington's Disease. London: W. B. Saunders

Hartmann, A., Hunot, S., Michel, P. P.et al. (2000). Caspase-3: a vulnerability factor and final effector in apoptotic death of dopaminergic neurons in Parkinson's disease. Proc. Natl. Acad. Sci., 97, 2875–80CrossRef Google Scholar PubMed

Hartmann, A., Michel, P. P., Troadec, J.-D.et al. (2001). Is Bax a mitochondrial mediator in apoptotic death of dopaminergic neurons in Parkinson's disease?J. Neurochem., 76, 1785–93CrossRef Google Scholar

Hayward, C., Colville, S., Swingler, R. J., and Brock, D. J. H. (1999). Molecular genetic analysis of the APEX nuclease gene in amyotrophic lateral sclerosis. Neurology, 52, 1899–901CrossRef Google Scholar PubMed

He, Y., Lee, T., and Leong, S. K. (2000). 6-hydroxydopamine induced apoptosis of dopaminergic cells in the rat substantia nigra. Brain Res., 858, 163–6CrossRef Google Scholar PubMed

Hegde, R., Srinivasula, S. M., Zhang, Z.et al. (2002). Identification of Omi/HtrA2 as a mitochondrial apoptotic serine protease that disrupts inhibitor of apoptosis protein-caspase interaction. J. Biol. Chem., 277, 432–8CrossRef Google Scholar PubMed

Hetman, M., Kanning, K., Cavanaugh, J. E., and Xia, Z. (1999). Neuroprotection by brain-derived neurotrophic factor is mediated by extracellular signal-regulated kinase and phosphatidylinositol 3-kinase. J. Biol. Chem., 2744, 22569–80CrossRef Google Scholar

Hirsch, T., Marchetti, P., Susin, S. A.et al. (1997). The apoptosis-necrosis paradox. Apoptogenic proteases activated after mitochondrial permeability transition determine the mode of cell death. Oncogene, 15, 1573–81CrossRef Google Scholar PubMed

Hodgson, J. G., Agopyan, N., Gutekunst, C. A.et al. (1999). A YAC mouse model for Huntington's disease with full-length mutant huntingtin, cytoplasmic toxicity, and selective striatal neurodegeneration. Neuron, 23, 181–92CrossRef Google Scholar PubMed

Holcik, M. (2002). The IAP proteins. Trends Gen., 18, 537–8CrossRef Google Scholar PubMed

Holcik, M., Thompson, C. S., Yaraghi, Z., Lefebvre, C. A., MacKenzie, A. E., and Korneluk, R. G. (1999). The hippocampal neurons of neuronal apoptosis inhibitory protein 1 (NAIP1)-deleted mice display increased vulnerability to kainic acid-induced injury. Proc. Natl. Acad. Sci. USA, 97, 2286–90CrossRef Google Scholar

Holzer, M., Gartner, U., Klinz, F. J., Narz, F., Heumann, R., and Arendt, T. (2001). Activation of mitogen-activated protein kinase cascade and phosphorylation of cytoskeletal proteins after neurone-specific activation of p21ras. I. Mitogen-activated protein kinase cascade. Neuroscience, 105, 1031–40CrossRef Google Scholar PubMed

Hu, Y., Benedict, M. A., Wu, D., Inohara, N., and Núñez, G. (1998). Bcl-xL interacts with Apaf-1 and inhibits Apaf-1-dependent caspase-9 activation. Proc. Natl. Acad. Sci. USA, 95, 4386–91CrossRef Google Scholar PubMed

The Huntington's Disease Collaborative Research Group (1993). A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell, 72, 971–83CrossRef

Ikonomidou, C., Qin, Y. Q., Labruyere, J., and Olney, J. W. (1996). Motor neuron degeneration induced by excitotoxin agonists has features in common with those seen in the SOD-1 transgenic mouse model of amyotrophic lateral sclerosis. J. Neuropathol. Exp. Neurol., 55, 211–44CrossRef Google Scholar PubMed

Inbal, B., Bialik, S., Sabanay, I., Shani, G., and Kimchi, A. (2002). DAP kinase and DRP-1 mediate membrane blebbing and the formation of autophagic vesicles during programmed cell death. J. Cell Biol., 157, 455–68CrossRef Google Scholar PubMed

Irizarry, M. C., McNamara, M., Fedorchak, K., Hsiao, K., and Hyman, B. T. (1997). APPSw transgenic mice develop age-related A beta deposits and neuropil abnormalities, but no neuronal loss in CA1. J. Neuropathol. Exp. Neurol., 56, 965–73CrossRef Google Scholar PubMed

Ishikawa, Y. and Kitamura, M. (1999). Dual potential of extracellular signal-regulated kinase for the control of cell survival. Biochem. Biophys. Res. Comm., 2644, 696–701CrossRef Google Scholar

Iwata, A., Maruyama, M., Kanazawa, I., and Nukina, N. (2001). α-synuclein affects the MAPK pathway and accelerates cell death. J. Biol. Chem., 276, 45320–9CrossRef Google Scholar PubMed

Jellinger, K. A. (1999). Is there apoptosis in Lewy body disease?Acta. Neuropathol., 97, 413–15CrossRef Google Scholar PubMed

Johnson, M. D., Kinoshita, Y., Xiang, H., Ghatan, S., and Morrison, R. S. (1999). Contribution of p53-dependent caspase activation to neuronal cell death declines with neuronal maturation. J. Neurosci., 19, 2996–3006CrossRef Google Scholar PubMed

Jones, J. M., Datta, P., Srinivasula, S. M.et al. (2003). Loss of Omi mitochondrial protease activity causes the neuromuscular disorder of mnd2 mutant mice. Nature, 425, 721–7CrossRef Google Scholar PubMed

Jost, C. A., Marin, M. C., and Kaelin, W. G. (1997). p73 is a human p53-related protein that can induce apoptosis. Nature, 389, 191–4CrossRef Google Scholar PubMed

Kalaria, R. N. (2003). Dementia comes of age in the developing world. Lancet, 361, 888–9CrossRef Google Scholar PubMed

Kaplan, D. R. and Miller, F. D. (1997). Signal transduction by the neurotrophin receptors. Curr. Opin. Cell Biol., 9, 213–21CrossRef Google Scholar PubMed

Katzman, R. (1993). Education and the prevalence of dementia and Alzheimer's disease. Neurology, 43, 13–20CrossRef Google Scholar PubMed

Keilin, D. (1930). Cytochrome and intracellular oxidase. Proc. R. Soc. Lond., 106, 418–44CrossRef Google Scholar

Kemp, J. A. and McKernan, R. M. (2002). NMDA receptor pathways as drug targets. Nat. Neurosci. (suppl), 5, 1039–42CrossRef Google Scholar PubMed

Kerr, J. F. R., Wyllie, A. H., and Currie, A. R. (1972). Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br. J. Cancer, 26, 239–57CrossRef Google Scholar PubMed

Kim, J. A., Mitsukawa, K., Yamada, M. K., Nishiyama, N., Matsuki, N., and Ikegaya, Y. (2002). Cytoskeleton disruption causes apoptotic degeneration of dentate granule cells in hippocampal slice cultures. Neuropharmacology, 42, 1109–18CrossRef Google Scholar PubMed

Kim, M., Lee, H. S., LaForet, G.et al. (1999). Mutant huntingtin expression in clonal striatal cells: dissociation of inclusion formation and neuronal survival by caspase inhibition. J. Neurosci., 19, 964–73CrossRef Google Scholar PubMed

Kim, T.-W., Pettingell, W. H., Jung, Y.-K., Kovacs, D. M., and Tazi, R. E. (1997). Alternative cleavage of Alzheimer-associated presenilins during apoptosis by a caspase-3 family protein. Science, 277, 373–6CrossRef Google Scholar

Kisby, G. E., Miline, J., and Sweatt, C. (1997). Evidence of reduced DNA repair in amyotrophic lateral sclerosis brain tissue. NeuroReport, 8, 1337–40CrossRef Google Scholar PubMed

Kitamura, Y., Shimohama, S., Kamoshima, W., Matsuoka, Y., Nomura, Y., and Taniguchi, T. (1997). Changes of p53 in the brains of patients with Alzheimer's disease. Biochem. Biophys. Res. Comm., 232, 418–21CrossRef Google Scholar PubMed

Kitamura, Y., Shimohama, S., Kamoshima, W.et al. (1998). Alteration of proteins regulating apoptosis, Bcl-2, Bcl-x, Bax, Bak, Bad, ICH-1 and CPP32, in Alzheimer's disease. Brain Res., 780, 260–9CrossRef Google Scholar PubMed

Klein, J. A., Longo-Guess, C. M., Rossmann, M. P.et al. (2002). The harlequin mouse mutation downregulates apoptosis-inducing factor. Nature, 419, 367–74CrossRef Google Scholar PubMed

Klionsky, D. J. and Emr, S. D. (2000). Autophagy as a regulated pathway of cellular degradation. Science, 290, 1717–21CrossRef Google Scholar PubMed

Kluck, R. M., Bossy-Wetzel, E., Green, D. R., and Newmeyer, D. D. (1997). The release of cytochrome c from mitochondria: a primary site for bcl-2 regulation of apoptosis. Science, 275, 1132–6CrossRef Google Scholar PubMed

Kosik, K. S., Joachim, C. L., and Selkoe, D. J. (1986). Microtubule-associated protein tau is a major antigenic component of paired helical filaments in Alzheimer's disease. Proc. Natl. Acad. Sci. USA, 83, 4044–8CrossRef Google Scholar

Kostic, V., Jackson-Lewis, V., Bilbao, F., Dubois-Dauphin, M., and Przedborski, S. (1997). Bcl-2: prolonging life in a transgenic mouse model of familial amyotrophic lateral sclerosis, Science, 277, 559–62CrossRef Google Scholar

Kuida, K., Haydar, T. F., Kuan, C.-Y.et al. (1998). Reduced apoptosis and cytochrome c-mediated caspase activation in mice lacking caspase-9. Cell, 94, 325–37CrossRef Google Scholar PubMed

Kuntz, C., Kinoshita, Y., Beal, M. F., Donehower, L. A., and Morrison, R. S. (2000). Absence of p53: no effect in a transgenic mouse model of familial amyotrophic lateral sclerosis. Exp. Neurol., 165, 184–90CrossRef Google Scholar

Kuperstein, F. and Yavin, E. (2002). ERK activation and nuclear translocation in amyloid-beta peptide- and iron-stressed neuronal cell cultures. Eur. J. Neurosci., 16, 44–54CrossRef Google Scholar PubMed

Kure, S., Tominaga, T., Yoshimoto, T., Tada, K., and Narisawa, K. (1991). Glutamate triggers internucleosomal DNA cleavage in neuronal cells. Biochem. Biophys. Res. Commun., 179, 39–45CrossRef Google Scholar PubMed

Kwon, C. H., Zhu, X., Zhang, J.et al. (2001). Pten regulates neuronal soma size: a mouse model of Lhermitte–Duclos disease. Nat. Genet., 29, 410–11CrossRef Google Scholar PubMed

LaCasse, E. C., Baird, S., Korneluk, R. G., and MacKenzie, A. E. (1998). The inhibitors of apoptosis (IAPs) and their emerging role in cancer. Oncogene, 17, 3247–59CrossRef Google Scholar

Lachyankar, M. B., Condon, P. J., Quesenberry, P. J.et al. (2000). A role for nuclear PTEN in neuronal differentiation. J. Neurosci., 20, 1404–13CrossRef Google Scholar PubMed

LaFerla, F. M., Hall, C. K., Ngo, L., and Jay, G. (1996). Extracellular deposition of β-amyloid upon p53-dependent neuronal cell death in transgenic mice. J. Clin. Invest., 98, 1626–32CrossRef Google Scholar PubMed

Lambrechts, D., Storkebaum, E., Morimoto, M.et al. (2003). VEGF is a modifier of amyotrophic lateral sclerosis in mice and humans and protects motoneurons against ischemic death. Nat. Gen., 34, 383–94CrossRef Google Scholar PubMed

Lashley, K. S. (1941). Thalamo-cortical connections of the rat's brain. J. Comp. Neurol., 75, 67–121CrossRef Google Scholar

LeBlanc, A., Liu, H., Goodyer, C., Bergeron, C., and Hammond, J. (1999). Caspase-6 role in apoptosis of human neurons, amyloidogenesis, and Alzheimer's disease. J. Biol. Chem., 274, 23426–36CrossRef Google Scholar PubMed

Leist, M., Single, B., Castoldi, A. F., Kühnle, S., and Nicotera, P. (1997). Intracellular adenosine triphosphate (ATP) concentration: a switch in the decision between apoptosis and necrosis. J. Exp. Med., 185, 1481–6CrossRef Google Scholar PubMed

Lennon, S. V., Martin, S. J., and Cotter, T. G. (1991). Dose-dependent induction of apoptosis in human tumour cell lines by widely diverging stimuli. Cell Prolif., 24, 203–14CrossRef Google Scholar PubMed

Leppin, C., Finiels-Marlier, F., Crawley, J. N., Montpied, P., and Paul, S. M. (1992). Failure of a protein synthesis inhibitor to modify glutamate receptor-mediated neurotoxicity in vivo. Brain Res., 581, 168–70CrossRef Google Scholar PubMed

Lesuisse, C. and Martin, L. J. (2002). Immature and mature neurons engage different apoptotic mechanisms involving caspase-3 and the mitogen-activated protein kinase pathway. J. Cereb. Blood Flow Metabol., 22, 935–50CrossRef Google Scholar PubMed

Letai, A., Bassik, M. C., Walensky, L. D., Sorcinelli, M. D., Weiler, S., and Korsmeyer, S. J. (2002). Distinct BH3 domains either sensitize or activate mitochondrial apoptosis, serving as prototype cancer therapeutics. Cancer Cell, 2, 183–92CrossRef Google Scholar PubMed

Levrero, M., Laurenzi, V., Costanzo, A.et al. (2000). The p53/p63/p73 family of transcription factors: overlapping and distinct functions. J. Cell Sci., 113, 1661–70Google Scholar PubMed

Lewis, J., Dickson, D. W., Lin, W. L.et al. (2001). Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP. Science, 293, 1487–91CrossRef Google Scholar PubMed

Li, H., Zhu, H., Xu, C.-J., and Yuan, J. (1998). Cleavage of Bid by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell, 94, 491–501CrossRef Google Scholar

Li, M., Ona, V. O., Guegan, C.et al. (2000). Functional role of caspase-1 and caspase-3 in an ALS transgenic mouse model. Science, 288, 283–4CrossRef Google Scholar

Li, P., Nijhawan, D., Budihardjo, I.et al. (1997). Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell, 91, 479–89CrossRef Google Scholar PubMed

Liange, X. H., Kleeman, L. K., Jiang, H. H.et al. (1998). Protection against fatal Sindbis virus encephalitis by beclin, a novel Bcl-2-interacting protein. J. Virol., 72, 8586–96Google Scholar

Lieberman, A. R. (1971). The axon reaction: a review of the principal features of perikaryal responses to axon injury. Int. Rev. Neurobiol., 14, 49–124CrossRef Google Scholar PubMed

Lipton, S. A. and Rosenberg, P. A. (1994). Excitatory amino acids as a final common pathway for neurologic disorders. N. Engl. J. Med., 330, 613–22Google Scholar PubMed

Liston, P., Roy, N., Tamai, K.et al. (1996). Suppression of apoptosis in mammalian cells by NAIP and a related family of IAP genes. Nature, 379, 349–53CrossRef Google Scholar

Lithgow, T., Driel, R., Bertram, J. F., and Strasser, A. (1994). The protein product of the oncogene bcl-2 is a component of the nuclear envelope, the endoplasmic reticulum, and the outer mitochondrial membrane. Cell Growth Differ., 5, 411–17Google Scholar PubMed

Liu, X., Kim, C. N., Yang, J., Jemmerson, R., and Wang, X. (1996). Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell, 86, 147–57CrossRef Google Scholar PubMed

Liu, X., Zou, H., Slaughter, C., and Wang, X. (1997). DFF, a heterodimeric protein that functions downstream of caspase-3 to trigger DNA fragmentation during apoptosis. Cell, 89, 175–84CrossRef Google Scholar PubMed

Liu, Z., Gastard, M., Verina, T., Bora, S., Mouton, P. R., and Koliatsos, V. E. (2001). Estrogens modulate experimentally induced apoptosis of granule cells in the adult hippocampus. J. Comp. Neurol., 441, 1–8CrossRef Google Scholar PubMed

Lockshin, R. A. and Williams, C. M. (1964). Programmed cell death: II. Endocrine potentiation of the breakdown of the intersegmental muscles of silkmoths. J. Insect. Physiol., 10, 643–9CrossRef Google Scholar

Lockshin, R. A. and Zakeri, Z. (2001). Programmed cell death and apoptosis: origins of the theory. Nat. Rev. Mol. Cell Biol., 2, 545–50CrossRef Google Scholar

Lockshin, R. A. and Zakeri, Z. (2002). Caspase-independent cell deaths. Curr. Opin. Cell Biol., 14, 727–33CrossRef Google Scholar PubMed

Lok, J. and Martin, L. J. (2002). Rapid subcellular redistribution of Bax precedes caspase-3 and endonuclease activation during excitotoxic neuronal apoptosis in rat brain. J. Neurotrauma, 19, 815–28CrossRef Google Scholar PubMed

Loo, D. T., Copani, A., Pike, C. J., Whittemore, E. R., Walencewicz, A. J., and Cotman, C. W. (1993). Apoptosis is induced by β-amyloid in cultured central nervous system neurons. Proc. Natl. Acad. Sci. USA, 90, 7951–5CrossRef Google Scholar PubMed

Lucas, D. R. and Newhouse, J. P. (1957). The toxic effect of sodium L-glutamate on the inner layers of the retina. Arch. Ophthal., 58, 193–201CrossRef Google Scholar PubMed

Lucassen, P. J., Chung, W. C. J., Kamphorst, W., and Swaab, D. F. (1997). DNA damage distribution in the human brain as shown by in situ end labeling: area-specific differences in aging and Alzheimer's disease in the absence of apoptotic morphology. J. Neuropathol. Exp. Neurol., 56, 887–900CrossRef Google Scholar PubMed

Majno, G. and Joris, I. (1995). Apoptosis, oncosis, and necrosis. An overview of cell death. Am. J. Pathol., 146, 3–15Google Scholar PubMed

Maki, C. G., Huibregtse, J. M., and Howley, P. M. (1996). In vivo ubiquitination and proteasome-mediated degradation of p53. Cancer Res., 56, 2649–54Google Scholar PubMed

Martin, L. J. (1999). Neuronal death in amyotrophic lateral sclerosis is apoptosis: possible contribution of a programmed cell death mechanism. J. Neuropathol. Exp. Neurol., 58, 459–71CrossRef Google Scholar PubMed

Martin, L. J. (2000). p53 is abnormally elevated and active in the CNS of patients with amyotrophic lateral sclerosis. Neurobiol. Dis., 7, 613–22CrossRef Google Scholar PubMed

Martin, L. J. (2001). Neuronal cell death in nervous system development, disease, and injury. Int. J. Mol. Med., 7, 455–78Google Scholar PubMed

Martin, L. J. and Liu, Z. (2002). Injury-induced spinal motor neuron apoptosis is preceded by DNA single-strand breaks and is p53- and Bax-dependent. J. Neurobiol., 50, 181–97CrossRef Google Scholar PubMed

Martin, L. J., Al-Abdulla, N. A., Brambrink, A. M., Kirsch, J. R., Sieber, F. E. and Portera-Cailliau, C. (1998). Neurodegeneration in excitotoxicity, global cerebral ischemia, and target deprivation: a perspective on the contributions of apoptosis and necrosis. Brain Res. Bull., 46, 281–309CrossRef Google Scholar PubMed

Martin, L. J., Kaiser, A., and Price, A. C. (1999). Motor neuron degeneration after sciatic nerve avulsion in adult rat evolves with oxidative stress and is apoptosis. J. Neurobiol., 40, 185–2013.0.CO;2-#>CrossRef Google Scholar PubMed

Martin, L. J., Kaiser, A., Yu, J. W., Natale, J. E., and Al-Abdulla, N. A. (2001). Injury-induced apoptosis of neurons in adult brain is mediated by p53-dependent and p53-independent pathways and requires Bax. J. Comp. Neurol., 433, 299–311CrossRef Google Scholar PubMed

Martin, L. J., Pardo, C. A., Cork, L. C., and Price, D. L. (1994). Synaptic pathology and glial responses to neuronal injury precede the formation of senile plaques and amyloid deposits in the aging cerebral cortex. Am. J. Pathol., 145, 1358–81Google Scholar PubMed

Martin, L. J., Price, A. C., McClendon, K. B.et al. (2003). Early events of target deprivation/axotomy-induced neuronal apoptosis in vivo: oxidative stress, DNA damage, p53 phosphorylation and subcellular redistribution of death proteins. J. Neurochem., 85, 234–47CrossRef Google Scholar PubMed

Martin, L. J., Sieber, F. E., and Traystman, R. J. (2000a). Apoptosis and necrosis occur in separate neuronal populations in hippocampus and cerebellum after ischemia and are associated with alterations in metabotropic glutamate receptor signaling pathways. J. Cereb. Blood Flow Metab., 20, 153–67CrossRef Google Scholar

Martin, L. J., Price, A. C., Kaiser, A., Shaikh, A. Y., and Liu, Z. (2000b). Mechanisms for neuronal degeneration in amyotrophic lateral sclerosis and in models of motor neuron death. Int. J. Mol. Med., 5, 3–13Google Scholar

Martinou, J.-C., Dubois-Dauphin, M., Staple, J. K.et al. (1994). Overexpression of bcl-2 in transgenic mice protects neurons from naturally occurring cell death and experimental ischemia. Neuron, 13, 1017–30CrossRef Google Scholar PubMed

Marzo, I., Brenner, C., Zamzami, N.et al. (1998). Bax and adenine nucleotide translocator cooperate in the mitochondrial control of apoptosis. Science, 281, 2027–31CrossRef Google Scholar

Mate, M. J., Ortiz-Lombardia, M., Boitel, B.et al. (2002). The crystal structure of the mouse apoptosis-inducing factor AIF. Nature Struct. Biol., 9, 442–6CrossRef Google Scholar PubMed

Mattson, M. P., Cheng, B., Davis, D., Bryant, K., Lieberburg, I., and Rydel, R. E. (1992). β-amyloid peptides destabilize calcium homeostasis and render human cortical neurons vulnerable to excitoxicity. J. Neurosci., 12, 376–89CrossRef Google Scholar

McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., and Stadlan, E. M. (1984). Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA work group under the auspices of the Department of Health and Human Services task force on Alzheimer's disease. Neurology, 34, 939–44CrossRef Google Scholar PubMed

McPhail, L. T., Vanderluit, J. L., McBride, C. B.et al. (2003). Endogenous expression of inhibitor of apoptosis proteins in facial motoneurons of neonatal and adult rats following axotomy. Neuroscience, 117, 567–75CrossRef Google Scholar PubMed

Merry, D. E. and Korsmeyer, S. J. (1997). Bcl-2 gene family in the nervous system. Ann. Rev. Neurosci., 20, 245–67CrossRef Google Scholar

Michaelidis, T. M., Sendtner, M., Cooper, J. D.et al. (1996). Inactivation of bcl-2 results in progressive degeneration of motoneurons, sympathetic and sensory neurons during early postnatal development. Neuron, 17, 75–89CrossRef Google Scholar PubMed

Migheli, A., Atzori, C., Piva, R.et al. (1999). Lack of apoptosis in mice with ALS. Nature Med., 5, 966–7CrossRef Google Scholar PubMed

Miller, T. M., Moulder, K. L., Knudson, C. M.et al. (1997). Bax deletion further orders the cell death pathway in cerebellar granule cells and suggests a caspase-independent pathway to cell death. J. Cell Biol., 139, 205–17CrossRef Google Scholar PubMed

Mizushima, N., Ohsumi, Y., and Yoshimori, T. (2002). Autophagosome formation in mammalian cells. Cell Struct. Funct., 27, 421–9CrossRef Google Scholar PubMed

Morishima, Y., Gotoh, Y., Zieg, J.et al. (2001). β-amyloid induces neuronal apoptosis via a mechanism that involves the c-Jun N-terminal kinase pathway and the induction of Fas ligand. J. Neurosci., 21, 7551–60CrossRef Google Scholar

Mouton, P. R., Martin, L. J., Calhoun, M. E., Dal Forno, G., and Price, D. L. (1998). Cognitive decline strongly correlates with cortical atrophy in Alzheimer's disease. Neurobiol. Aging, 19, 371–7CrossRef Google Scholar

Muchmore, S. W., Sattler, M., Liang, H.et al. (1999). X-ray and NMR structure of human Bcl-xL, an inhibitor of programmed cell death. Nature, 381, 335–41CrossRef Google Scholar

Mund, T., Gewies, A., Schoenfield, N., Bauer, M. K. A., and Grimm, S. (2003). Spike, a novel BH3-only protein, regulates apoptosis at the endoplasmic reticulum. FASEB J. (February 19). 10.1096/fj.02-0657fjeCrossRef

Nagata, S. (1999). Fas ligand-induced apoptosis. Annu. Rev. Genet., 33, 29–55CrossRef Google Scholar PubMed

Nakagawa, T., Zhu, H., Morishima, N.et al. (2000). Caspase-12 mediates endoplasmic reticulum-specific apoptosis and cytotoxicity by amyloid-beta. Nature, 403, 98–103CrossRef Google Scholar PubMed

Nakajima, W., Ishida, A., Lange, M. S.et al. (2000). Apoptosis has a prolonged role in the neurodegeneration after hypoxic ischemia in the newborn rat. J. Neurosci., 20, 7994–8004CrossRef Google Scholar

Naruse, S., Igarashi, S., Kobayashi, H.et al. (1991). Mis-sense mutation Val→Ile in exon 17 of amyloid precursor protein gene in Japanese familial Alzheimer's disease. Lancet., 337, 978–9CrossRef Google Scholar PubMed

Natale, J. E., Cheng, Y., and Martin, L. J. (2002). Thalamic neuron apoptosis emerges rapidly after cortical damage in immature mice. Neuroscience, 112, 665–76CrossRef Google Scholar PubMed

Nechushtan, A., Smith, C. L., Lamensdorf, I., Yoon, S.-H., and Youle, R. J. (2001). Bax and Bak coalesce into novel mitochondria-associated clusters during apoptosis. J. Cell Biol., 153, 1265–76CrossRef Google Scholar PubMed

Nicholson, S. J., Witherden, A. S., Hafezparast, M., Martin, J. E., and Fisher, E. M. C. (2000). Mice, the motor system, and human motor neuron pathology. Mamm. Genome, 11, 1041–52CrossRef Google Scholar PubMed

Northington, F. J., Ferriero, D. M., Graham, E. M., Traystman, R. J., and Martin, L. J. (2001). Early neurodegeneration after hypoxia-ischemia in neonatal rat is necrosis while delayed neuronal death is apoptosis. Neurobiol. Dis., 8, 207–19CrossRef Google Scholar PubMed

O'Connor, T. M. and Wyttenbach, C. R. (1974). Cell death in the embryonic chick spinal cord. J. Cell Biol., 60, 448–59CrossRef Google Scholar PubMed

Oddo, S., Caccamo, A., Shepherd, J. D.et al. (2003). Triple-transgenic model of Alzheimer's disease with plaques and tangles: intracellular Aβ and synaptic dysfunction. Neuron, 39, 409–21CrossRef Google Scholar PubMed

Offen, D., Beart, P. M., Cheung, N. S.et al. (1998). Transgenic mice expressing human Bcl-2 in their neurons are resistant to 6-hydroxydopamine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity. Proc. Natl. Acad. Sci., 95, 5789–94CrossRef Google Scholar PubMed

Ogier-Denis, E. and Codogno, P. (2003). Autophagy: a barrier or an adaptive response to cancer. Biochim. Biophys. Acta., 1603, 113–28Google Scholar PubMed

Olanow, C. W. and Tatton, W. G. (1999). Etiology and pathogenesis of Parkinson's disease. Ann. Rev. Neurosci., 22, 123–44CrossRef Google Scholar PubMed

Olkowski, Z. L. (1998). Mutant AP endonuclease in patients with amyotrophic lateral sclerosis. NeuroReport, 9, 239–42CrossRef Google Scholar PubMed

Olney, J. W. (1971). Glutamate-induced neuronal necrosis in the infant mouse hypothalamus. An electron microscopic study. J. Neuropathol. Exp. Neurol., 30, 75–90CrossRef Google Scholar PubMed

Olshansky, S. J., Carnes, B. A., and Cassel, C. K. (1993). The aging of the human species. Sci. Am., 268, 46–52CrossRef Google Scholar PubMed

Orrenius, S., Zhivotovsky, B., and Nicotera, P. (2003). Regulation of cell death: the calcium-apoptosis link. Nat. Rev., 4, 552–65CrossRef Google Scholar PubMed

Paradis, E., Douillard, H., Koutroumanis, M., Goodyer, C., and LeBlanc, A. (1997). Amyloid β peptide of Alzheimer's disease downregulates Bcl-2 and upregulates Bax expression in human neurons. J. Neurosci., 16, 7533–9CrossRef Google Scholar

Passer, B. J., Pellegrini, L., Vito, P., Ganjei, J. K., and D'Adamio, L. (1999). Interaction of Alzheimer's presenilin-1 and presenilin-2 with Bcl-X(L). A potential role in modulating the threshold of cell death. J. Biol. Chem., 274, 24007–13CrossRef Google Scholar PubMed

Patrick, G. N., Zukerberg, L., Nikolic, M., Monte, S., Dikkes, P., and Tsai, L. H. (1999). Conversion of p35 to p25 deregulates Cdk5 activity and promotes neurodegeneration. Nature, 402, 615–22CrossRef Google Scholar PubMed

Pelvig, D. P., Pakkenberg, H., Regeur, L., Oster, S., and Pakkenberg, B. (2003). Neocortical glial cell numbers in Alzheimer's disease. A stereological study. Dement. Geriatr. Cogn. Disord., 16, 212–19CrossRef Google Scholar PubMed

Perrelet, D., Ferri, A., Liston, P., Muzzini, P., Korneluk, R. G., and Kato, A. C. (2002). IAPs are essential for GDNF-mediated neuroprotective effects in injured motor neuron in vivo. Nat. Cell Biol., 4, 175–9CrossRef Google Scholar PubMed

Petersen, A., Larsen, K. E., Behr, G. G.et al. (2001). Expanded CAG repeats in exon 1 of the Huntington's disease gene stimulate dopamine-mediated striatal neuron autophagy and degeneration. Hum. Mol. Genet., 10, 1243–54CrossRef Google Scholar PubMed

Pilar, G. and Landmesser, L. (1976). Ultrastructural differences during embryonic cell death in normal and peripherally deprived ciliary ganglia. J. Cell Biol., 68, 339–56CrossRef Google Scholar PubMed

Pompl, P. N., Yemul, S., Xiang, Z.et al. (2003). Caspase gene expression in the brain as a function of the clinical progression of Alzheimer's disease. Arch. Neurol., 60, 369–76CrossRef Google Scholar

Poorkaj, P., Bird, T. D., Wijsman, E.et al. (1998). Tau is a candidate gene for chromosome 17 frontotemporal dementia. Ann. Neurol., 43, 815–25CrossRef Google Scholar PubMed

Portera-Cailliau, C., Price, D. L., and Martin, L. J. (1997a). Excitotoxic neuronal death in the immature brain is an apoptosis-necrosis morphological continuum. J. Comp. Neurol., 378, 70–87Google Scholar

Portera-Cailliau, C., Price, D. L., and Martin, L. J. (1997b). Non-NMDA and NMDA receptor-mediated excitotoxic neuronal deaths in adult brain are morphologically distinct: further evidence for an apoptosis-necrosis continuum. J. Comp. Neurol., 378, 88–1043.0.CO;2-G>CrossRef Google Scholar

Pozniak, C. D., Radinovic, S., Yang, A., McKeon, F., Kaplan, D. R., and Miller, F. D. (2000). An anti-apoptotic role for the p53 family member, p73, during developmental neuron death. Science, 289, 304–6CrossRef Google Scholar PubMed

Prestige, M. (1970). Differentiation, degeneration, and the role of the periphery: quantitative considerations. In The Neurosciences: Second Study Program, ed. F. O. Schmitt. New York: Rockefeller University Press, pp. 73–82

Proskuryakov, S. Y., Konoplyannikov, A. G., and Gabai, V. L. (2003). Necrosis: a specific form of programmed cell death. Exp. Cell Res., 283, 1–16CrossRef Google Scholar PubMed

Prudlo, J., Koenig, J., Graser, J.et al. (2000). Motor neuron cell death in a mouse model of FALS is not mediated by the p53 cell survival regulator. Brain Res., 897, 183–7CrossRef Google Scholar

Putcha, G. V., Deshmukh, M., and Johnson, E. M. Jr. (1999). Bax translocation is a critical event in neuronal apoptosis: regulation by neuroprotectants, Bcl-2, and caspases. J. Neurosci., 19, 7476–85CrossRef Google Scholar PubMed

Raffray, M. and Cohen, G. M. (1997). Apoptosis and necrosis in toxicology: a continuum or distinct modes of cell death?Pharmacol. Ther., 75, 153–77CrossRef Google Scholar PubMed

Raoul, C., Estvez, A. G., Nishimune, H.et al. (2002). Motoneuron death triggered by a specific pathway downstream of Fas: potentiation by ALS-linked SOD1 mutations. Neuron, 35, 1067–83CrossRef Google Scholar PubMed

Rapoport, M., Dawson, H. N., Binder, L. I., Vitek, M. P., and Ferreira, A. (2002). Tau is essential to β-amyloid-induced neurotoxicity. Proc. Natl. Acad. Sci. USA, 99, 6364–9CrossRef Google Scholar PubMed

Rathke-Hartlieb, S., Schlomann, U., Heimann, P., Meisler, M. H., Jockusch, H., and Bartsch, J. W. (2002). Progressive loss of striatal neurons causes motor dysfunction in MND2 mutant mice and is not prevented by Bcl-2. Exp. Neurol., 175, 87–97CrossRef Google Scholar

Reddy, P. H., Williams, M., Charles, V.et al. (1998). Behavioral abnormalities and selective neuronal loss in HD transgenic mice expressing mutated full-length HD cDNA. Nat. Genet., 20, 198–202CrossRef Google Scholar

Robertson, J. D., Enoksson, M., Suomela, M., Zhivotovsky, B., and Orrenius, S. (2002). Caspase-2 acts upstream of mitochondria to promote cytochrome c release during etoposide-induced apoptosis. J. Biol. Chem., 277, 29803–9CrossRef Google Scholar PubMed

Robison, S. H., Tandan, R., and Bradley, W. G. (1993). Repair of N-methylpurines in DNA from lymphocytes of patients with amyotrophic lateral sclerosis. J. Neurol. Sci., 115, 201–7CrossRef Google Scholar PubMed

Rohn, T. T., Rissman, R. A., Davis, M. C., Kim, Y. E., Cotman, C. W., and Head, E. (2002). Caspase-9 activation and caspase cleavage of tau in the Alzheimer's disease brain. Neurobiol. Dis., 11, 341–54CrossRef Google Scholar PubMed

Romanes, G. J. (1946). Motor localization and the effects of nerve injury on the ventral horn cells of the spinal cord. J. Anat., 80, 117–31Google Scholar PubMed

Rosen, D. R., Siddique, T., Patterson, D.et al. (1993). Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature, 362, 59–62CrossRef Google Scholar PubMed

Rosenmann, H., Meiner, Z., Kahana, E.et al. (2003). An association study of the codon 72 polymorphism in the pro-apoptotic gene p53 and Alzheimer's disease. Neurosci. Lett., 340, 29–32CrossRef Google Scholar PubMed

Roses, A. D. (1996). Apolipoprotein E alleles as risk factors in Alzheimer's disease. Annu. Rev. Med., 47, 387–400CrossRef Google Scholar PubMed

Rothstein, J. D., Martin, L. J., and Kuncl, R. W. (1992). Decreased glutamate transport by the brain and spinal cord in amyotrophic lateral sclerosis. N. Engl. J. Med., 326, 1464–8CrossRef Google Scholar PubMed

Rothstein, J. D., Kammen, M., Levey, A. I., Martin, L. J., and Kuncl, R. W. (1995). Selective loss of glial glutamate transporter GLT-1 in amyotrophic lateral sclerosis. Ann. Neurol., 38, 73–84CrossRef Google Scholar PubMed

Rowland, L. P. and Shneider, N. A. (2001). Amyotrophic lateral sclerosis. N. Engl. J. Med., 344, 1688–700CrossRef Google Scholar PubMed

Roy, N., Mahadevan, M. S., McLean, M.et al. (1995). The gene for neuronal apoptosis inhibitory protein is partially deleted in individuals with spinal muscular atrophy. Cell, 80, 167–78CrossRef Google Scholar PubMed

Sakahira, H., Enari, M., Ohsawa, Y., Uchiyama, Y., and Nagata, S. (1999). Apoptotic nuclear morphological change without DNA fragmentation. Curr. Biol., 9, 543–6CrossRef Google Scholar PubMed

Sano, T., Lin, H., Chen, X.et al. (1999). Differential expression of MMAC/PTEN in glioblastoma multiforme: relationship to localization and prognosis. Cancer Res., 59, 1820–4Google Scholar PubMed

Sathasivam, S., Ince, P. G., and Shaw, P. J. (2001). Apoptosis in amyotrophic lateral sclerosis: a review of the evidence. Neuropathol. Appl. Neurobiol., 27, 257–74CrossRef Google Scholar

Satoh, T., Nakatsuka, D., Watanabe, Y., Nagata, I., Kikuchi, H., and Namura, S. (2000). Neuroprotection by MAPK/ERK kinase inhibition with U0126 against oxidative stress in a mouse neuronal cell line and rat primary cultured cortical neurons. Neurosci. Lett., 288, 163–6CrossRef Google Scholar

Saudou, F., Finkbeiner, S., Devys, D., and Greenberg, M. E. (1998). Huntingtin acts in the nucleus to induce apoptosis but death does not correlate with the formation of intranuclear inclusions. Cell, 95, 55–66CrossRef Google Scholar

Saunders, J. W. (1966). Death in embryonic systems. Science, 154, 604–12CrossRef Google Scholar PubMed

Schilling, G., Becher, M. W., Sharp, A. H.et al. (1999). Intranuclear inclusions and neuritic aggregates in transgenic mice expressing a mutant N-terminal fragment of huntingtin. Hum. Mol. Genet., 8, 397–407CrossRef Google Scholar PubMed

Schreiber, S. S., Tocco, G., Najm, I., Thompson, R. F., and Baudry, M. (1993). Cycloheximide prevents kainate-induced neuronal death and c-fos expression in adult rat brain. J. Mol. Neurosci., 4, 149–59CrossRef Google Scholar PubMed

Schwartz, L. M. and Milligan, C. E. (1996). Cold thoughts of death: the role of ICE proteases in neuronal cell death. Trends Neurosci., 19, 555–62CrossRef Google Scholar PubMed

Schwartz, L. M., Smith, S. W., Jones, M. E. E. M, and Osborne, B. A. (1993). Do all programmed cell deaths occur via apoptosis?Proc. Natl. Acad. Sci. USA, 90, 980–4CrossRef Google Scholar PubMed

Schweichel, J. U. and Merker, H. J. (1973). The morphology of various types of cell death in prenatal tissues. Teratology, 7, 253–66CrossRef Google Scholar PubMed

Scorrano, L., Oakes, S. A., Opferman, T. J.et al. (2003). Bax and Bak regulation of endoplasmic reticulum Ca2+: a control point for apoptosis. Science, 300, 135–9CrossRef Google Scholar PubMed

Selkoe, D. J. (2002). Alzheimer's disease is a synaptic failure. Science, 298, 789–91CrossRef Google Scholar PubMed

Selznick, L. A., Holtzman, D. M., Han, B. H.et al. (1999). In situ immunodetection of neuronal caspase-3 activation in Alzheimer's disease. J. Neuropath. Exp. Neurol., 58, 1020–6CrossRef Google Scholar

Shaikh, A. Y. and Martin, L. J. (2002). DNA base-excision repair enzyme apurinic/apyrimidinic endonuclease/redox factor-1 is increased and competent in brain and spinal cord of individuals with amyotrophic lateral sclerosis. NeuroMolecular Med., 2, 47–60CrossRef Google Scholar PubMed

Sherrington, R., Rogaev, E. I., Liang, Y.et al. (1995). Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease. Nature, 375, 754–60CrossRef Google Scholar PubMed

Shieh, S.-Y., Ikeda, M., Taya, Y., and Prives, C. (1997). DNA damage-induced phosphorylation of p53 alleviates inhibition by MDM2. Cell, 91, 325–34CrossRef Google Scholar PubMed

Shimizu, S., Ide, T., Yanagida, T., and Tsujimoto, Y. (2000). Electrophysiological study of a novel large pore formed by Bax and the voltage-dependent anion channel that is permeable to cytochrome c. J. Biol. Chem., 275, 12321–5CrossRef Google Scholar PubMed

Shimohama, S., Tanino, H., and Fujimoto, S. (2001). Differential subcellular localization of caspase family protein in the adult rat brain. Neurosci. Lett., 315, 125–8CrossRef Google Scholar PubMed

Simonian, N. A., Getz, R. L., Leveque, J. C., Konradi, C., and Coyle, J. T. (1996). Kainate induces apoptosis in neurons. Neuroscience, 74, 675–83CrossRef Google Scholar PubMed

Simons, M., Beinroth, S., Gleichmann, M.et al. (1999). Adenovirus-mediated gene transfer of inhibitors of apoptosis proteins delays apoptosis in cerebellar granule neurons. J. Neurochem., 72, 292–301CrossRef Google Scholar PubMed

Smale, G., Nichols, N. R., Brady, D. R., Finch, C. E., and Horten, W. E. Jr. (1995). Evidence for apoptotic cell death in Alzheimer's disease. Exp. Neurol., 133, 225–30CrossRef Google Scholar PubMed

Song, Q., Kuang, Y., Dixit, V. M., and Vincenz, C. (1999). Boo, a negative regulator of cell death, interacts with Apaf-1. EMBO J., 18, 167–78CrossRef Google Scholar PubMed

Srivastava, R. K., Sollott, S. J., Khan, L., Hansford, R., Lakatta, E. G., and Longo, D. L. (1999). Bcl-2 and Bcl-X(L) block thapsigargin-induced nitric oxide generation, c-Jun NH(2)-terminal kinase activity, and apoptosis. Mol. Cell Biol., 19, 5659–74CrossRef Google Scholar PubMed

Stadelmann, C., Deckwerth, T. L., Srinivasan, A., Bancher, C., Brock, W., and Lassmann, H. (1999). Activation of caspase-3 in single neurons and autophagic granules of granulovacuolar degeneration in Alzheimer's disease. Evidence for apoptotic cell death. Am. J. Pathol., 155, 1459–66CrossRef Google Scholar PubMed

Stanciu, M., Wang, Y., Kentor, R.et al. (2000). Persistent activation of ERK contributes to glutamate-induced oxidative toxicity in a neuronal cell line and primary cortical neuron cultures. J. Biol. Chem., 275, 12200–6CrossRef Google Scholar

Steffan, J. S., Kazantsev, A., Spasic-Boskovic, O.et al. (2000). The Huntington's disease protein interacts with p53 and CREB-binding protein and represses transcription. Proc. Natl. Acad. Sci. USA, 97, 6763–8CrossRef Google Scholar PubMed

Stennicke, H. R., Deveraux, Q. L., Humke, E. W., Reed, J. C., Dixit, V. M., and Salvesen, G. S. (1999). Caspase-9 can be activated without proteolytic processing. J. Biol. Chem., 274, 8359–62CrossRef Google Scholar PubMed

Su, J. H., Anderson, A. J., Cribbs, D. H.et al. (2003). Fas and Fas ligand are associated with neuritic degeneration in the AD brain and participate in β-amyloid-induced neuronal death. Neurobiol. Dis., 12, 182–93CrossRef Google Scholar PubMed

Su, J. H., Zhao, M., Anderson, A. J., Srinivasan, A., and Cotman, C. W. (2001). Activated caspase-3 expression in Alzheimer's and aged control brain: correlation with Alzheimer pathology. Brain Res., 898, 350–7CrossRef Google Scholar PubMed

Susin, S. A., Lorenzo, H. K., Zamzami, N.et al. (1999). Molecular characterization of mitochondrial apoptosis-inducing factor. Nature, 397, 441–6CrossRef Google Scholar PubMed

Sze, C.-I., Bi, H., Kleinschmidt-DeMasters, B. K., Filley, C. M., and Martin, L. J. (2001). N-Methyl-D-aspartate receptor subunit proteins and their phosphorylation status are altered selectively in Alzheimer's disease. J. Neurol. Sci., 182, 151–9CrossRef Google Scholar PubMed

Sze, C.-I., Troncoso, J. C., Kawas, C., Mouton, P., Price, D. L., and Martin, L. J. (1997). Loss of the presynaptic vesicle protein synaptophysin in hippocampus correlates with cognitive decline in Alzheimer's disease. J. Neuropathol. Exp. Neurol., 56, 933–94CrossRef Google Scholar

Takashima, A., Noguchi, K., Sato, K., Hoshino, T., and Imahori, K . (1993). Tau protein kinase I is essential for amyloid beta-protein-induced neurotoxicity. Proc. Natl. Acad. Sci. USA, 90, 7789–93CrossRef Google Scholar PubMed

Tandan, R., Robison, S. H., Munzer, J. S. and Bradley, W. G. (1987). Deficient DNA repair in amyotrophic lateral sclerosis cells. J. Neurol. Sci., 79, 189–203CrossRef Google Scholar PubMed

Tata, J. R. (1966). Requirement for RNA and protein synthesis for induced regression of tadpole tail in organ culture. Dev. Biol., 13, 77–94CrossRef Google Scholar PubMed

Tatton, N. A., MaClean-Fraser, A., Tatton, W. G., Perl, D. P., and Olnanow, C. W. (1998). A fluorescent double-labeling method to detect and confirm apoptotic nuclei in Parkinson's disease. Ann. Neurol., 44, S142–8CrossRef Google Scholar PubMed

Tatton, W. G., Chalmers-Redman, R., Brown, D., and Tatton, N. (2003). Apoptosis in Parkinson's disease: signals for neuronal degeneration. Ann. Neurol., 53, S61–72CrossRef Google Scholar

Tenneti, L. and Lipton, S. A. (2000). Involvement of activated caspase-3-like proteases in N-methyl-D-aspartate-induced apoptosis in cerebrocortical neurons. Ann. Neurol., 74, 134–42Google Scholar PubMed

Terry, R. D., Masliah, E., Salmon, D. P.et al. (1991). Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment. Ann. Neurol., 30, 572–80CrossRef Google Scholar PubMed

Tomkins, J., Dempster, S., Banner, S. J., Cookson, M. R., and Shaw, P. J. (2000). Screening of AP endonuclease as a candidate gene for amyotrophic lateral sclerosis. NeuroReport, 11, 1695–7CrossRef Google Scholar PubMed

Tompkins, M. M., Basgall, E. J., Zamrini, E., and Hill, W. D. (1997). Apoptotic-like changes in Lewy-body-associated disorders and normal aging in substantia nigra neurons. Am. J. Pathol., 150, 119–31Google Scholar

Torvik, A. (1976). Central chromatolysis and the axon reaction. A reappraisal. Neuropathol. Appl. Neurobiol., 2, 423–32CrossRef Google Scholar

Trimmer, P. A., Smith, T. S., Jung, A. B., and Bennett, J. P. Jr. (1996). Dopamine neurons from transgenic mice with a knockout of the p53 gene resist MPTP neurotoxicity. Neurodegeneration, 5, 233–9CrossRef Google Scholar PubMed

Troy, C. M., Friedman, J. E., and Friedman, W. J. (2002). Mechanisms of p75-mediated death of hippocampal neurons. Role of caspases. J. Biol. Chem., 277, 34295–302CrossRef Google Scholar PubMed

Trump, B. F. and Berezesky, I. K. (1996). The role of altered [Ca2+]i regulation in apoptosis, oncosis, and necrosis. Biochim. Biophys. Acta., 1313, 173–8CrossRef Google Scholar PubMed

Trump, B. J., Goldblatt, P. J., and Stowell, R. E. (1964). Studies on necrosis of mouse liver in vitro. Ultrastructural alterations in the mitochondria of hepatic parenchymal cells. Lab. Invest., 14, 343–71Google Scholar

Turmaine, M., Raza, A., Mahal, A., Mangiarini, L., Bates, G. P., and Davies, S. W. (2000). Nonapoptotic neurodegeneration in a transgenic mouse model of Huntington's disease. Proc. Natl. Acad. Sci. USA, 97, 8093–7CrossRef Google Scholar

Uberti, D., Carsana, T., Bernardi, E.et al. (2002). Selective impairment of p53-mediated cell death in fibroblasts from sporadic Alzheimer's disease patients. J. Cell Sci., 115, 3131–8Google Scholar PubMed

Uetsuki, T., Takemoto, K., Nishimura, I.et al. (1999). Activation of neuronal caspase-3 by intracellular accumulation of wild-type Alzheimer amyloid precursor protein. J. Neurosci., 19, 6955–64CrossRef Google Scholar PubMed

Uppuluri, S., Knipling, L., Sackett, D. L., and Wolff, J. (1993). Localization of the colchicine-binding site of tubulin. Proc. Natl. Acad. Sci. USA, 90, 11598–602CrossRef Google Scholar PubMed

Bekkum, D. W. (1957). The effect of x-rays on phosphorylations in vivo. Biochim. Biophys. Acta., 25, 487–92CrossRef Google Scholar

Vander Heiden, M. G., Chandel, N. S., Williamson, E. K., Schumacker, P. T., and Thompson, C. B. (1997). Bcl-xL regulates the membrane potential and volume homeostasis of mitochondria. Cell, 91, 627–37CrossRef Google Scholar PubMed

Gurp, M., Festjens, N., Loo, G., Saelens, X., and Vandenabeele, P. (2003). Mitochondrial intermembrane proteins in cell death. Biochem. Biophys. Res. Comm., 304, 487–97CrossRef Google Scholar PubMed

Lookeren Campagne, M., Lucassen, P. J., Vermeulen, J. P., and Balázs, R. (1995). NMDA and kainate induced internucleosomal DNA cleavage associated with both apoptotic and necrotic cell death in the neonatal rat brain. Eur. J. Neurosci., 7, 1627–40CrossRef Google Scholar PubMed

Verhagen, A. M., Ekert, P. G., Pakusch, M.et al. (2000). Identification of DIABLO, a mammalian protein that promotes apoptosis by binding to and antagonizing IAP proteins. Cell, 102, 43–53CrossRef Google Scholar PubMed

Verhagen, A. M., Silke, J., Ekert, P. G.et al. (2002). HtrA2 promotes cell death through its serine protease activity and its ability to antagonize inhibitor of apoptosis proteins. J. Biol. Chem., 277, 445–54CrossRef Google Scholar PubMed

Vila, M., Jackson-Lewis, V., Vukosavic, S.et al. (2001). Bax ablation prevents dopaminergic neurodegeneration in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease. Proc. Natl. Acad. Sci., 98, 2837–42CrossRef Google Scholar PubMed

Villunger, A., Michalak, E. M., Coultas, L.et al. (2003). p53- and drug-induced apoptotic responses mediated by BH3-only proteins Puma and Noxa. Science, 302, 1036–8CrossRef Google Scholar PubMed

Virchow, R. (1858). Cellular Pathology as Based Upon Physiological and Pathological Histology (Translation). London: Churchill

Vonsattel, J. P. and DiFiglia, M. (1998). Huntington's disease. J. Neuropathol. Exp. Neurol., 57, 369–84CrossRef Google Scholar

Vonsattel, J. P., Myers, R. H., Stevens, T. J., Ferrante, R. J., Bird, E. D., and Richardson, E. P. Jr. (1985). Neuropathological classification of Huntington's disease. J. Neuropathol. Exp. Neurol., 44, 559–77CrossRef Google Scholar PubMed

Vukosavic, S., Dubois-Dauphin, N., Romero, N., and Przedborski, S. (1999). Bax and Bcl-2 interaction in a transgenic mouse model of amyotrophic lateral sclerosis. J. Neurochem., 73, 2460–8CrossRef Google Scholar

Wang, H.-G., Pathan, N., Ethell, I. M.et al. (1999). Ca2+-induced apoptosis through calcineurin dephosphorylation of Bad. Science, 284, 339–43CrossRef Google Scholar PubMed

Wang, H.-G., Rapp, U. R., and Reed, J. C. (1996). Bcl-2 targets the protein kinase raf-1 to mitochondria. Cell, 87, 629–38CrossRef Google Scholar

Wei, M. C., Zong, W-X., Cheng, E. H.-Y.et al. (2001). Proapoptotic Bax and Bak: a requisite gateway to mitochondrial dysfunction and death. Science, 292, 727–30CrossRef Google Scholar PubMed

Weidemann, A., Paliga, K., Drrwang, U.et al. (1999). Proteolytic processing of the Alzheimer's disease amyloid precursor protein within its cytoplasmic domain by caspase-like proteases. J. Biol. Chem., 274, 5823–9CrossRef Google Scholar PubMed

West, M. J., Kawas, C. H., Martin, L. J., and Troncoso, J. C. (2000). The CA1 region of the human hippocampus is a hot spot in Alzheimer's disease. Ann. NY Acad. Sci., 908, 255–9CrossRef Google Scholar PubMed

White, E. and Prives, C. (1999). DNA damage enables p73. Nature, 399, 734–7CrossRef Google Scholar PubMed

Whitehouse, P. J., Price, D. L., Struble, R. G., Clark, A. W., Coyle, J. T., and DeLong, M. R. (1982). Alzheimer's disease and senile dementia: loss of neurons in the basal forebrain. Science, 215, 1237–9CrossRef Google Scholar PubMed

Widmann, C., Gerwins, P., Johnson, N., Jarpe, M. B., and Johnson, G. L. (1998). MEK kinase 1, a substrate for DEVD-directed caspases, is involved in genotoxin-induced apoptosis. Mol. Cell Biol., 18, 2416–29CrossRef Google Scholar PubMed

Wolf, B. B. and Green, D. R. (1999). Suicidal tendencies: apoptotic cell death by caspase family proteinases. J. Biol. Chem., 274, 20049–52CrossRef Google Scholar PubMed

Wolter, K. G., Hsu, Y.-T., Smith, C. L., Nechushtan, A., Xi, X.-G., and Youle, R. L. (1997). Movement of Bax from the cytosol to mitochondria during apoptosis. J. Cell Biol., 139, 1281–92CrossRef Google Scholar PubMed

Wong, P. C., Cai, H., Borchelt, D. R., and Price, D. L. (2002). Genetically engineered mouse models of neurodegenerative diseases. Nat. Neurosci., 5, 633–9CrossRef Google Scholar PubMed

Wong, P. C., Pardo, C. A., Borchelt, D. R.et al. (1995). An adverse property of a familial ALS-linked SOD1 mutation causes motor neuron disease characterized by vacuolar degeneration of mitochondria. Neuron, 14, 1105–16CrossRef Google Scholar PubMed

Wüllner, U., Kornhuber, J., Weller, M.et al. (1999). Cell death and apoptosis regulating proteins in Parkinson's disease – a cautionary note. Acta. Neuropathol., 97, 408–12Google Scholar PubMed

Wyllie, A. H. (1980). Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation. Nature, 284, 555–6CrossRef Google Scholar PubMed

Wyllie, A. H., Kerr, J. F. R., and Currie, A. R. (1980). Cell death: the significance of apoptosis. Int. Rev. Cytol., 68, 251–306CrossRef Google Scholar

Xanthoudakis, S. and Curran, T. (1992). Identification and characterization of Ref-1, a nuclear protein that facilitates AP-1 DNA-binding activity. EMBO J., 11, 653–65Google Scholar PubMed

Xiang, H., Kinoshita, Y., Knudson, C. M., Korsmeyer, S. J., Schwartzkroin, P. A., and Morrison, R. S. (1998). Bax involvement in p53-mediated neuronal cell death. J. Neurosci., 18, 1363–73CrossRef Google Scholar PubMed

Xu, D. G., Korneluk, R. G., Tamai, K.et al. (1997). Distribution of neuronal apoptosis inhibitory protein-like immunoreactivity in the rat central nervous system. J. Comp. Neurol., 382, 247–593.0.CO;2-3>CrossRef Google Scholar PubMed

Xu, J., Kao, S. Y., Lee, F. J., Song, W., Jin, L. W., and Yankner, B. A. (2002). Dopamine-dependent neurotoxicity of alpha-synuclein: a mechanism for selective neurodegeneration in Parkinson disease. Nat. Med., 8, 600–6CrossRef Google Scholar PubMed

Xue, L. Z., Fletcher, G. C., and Tolkovsky, A. M. (1999). Autophagy is activated by apoptotic signalling in sympathetic neurons: an alternative mechanism of death execution. Mol. Cell Neurosci., 14, 180–98CrossRef Google Scholar PubMed

Yaar, M., Zhai, S., Fine, R. E.et al. (2002). Amyloid β binds trimers as well as monomers of the 75-kDa neurotrophin receptor and activates receptor signaling. J. Biol. Chem., 277, 7720–5CrossRef Google Scholar PubMed

Yan, X. X., Najbauer, J., Woo, C. C., Dashtipour, K., Ribak, C. E., and Leon, M. (2001). Expression of active caspase-3 in mitotic and postmitotic cells or rat forebrain. J. Comp. Neurol., 433, 4–22CrossRef Google Scholar PubMed

Yang, A., Walker, N., Bronson, R.et al. (2000). p73-deficient mice have neurological, pheromonal and inflammatory defects but lack spontaneous tumors. Nature, 404, 99–103CrossRef Google Scholar

Yang, E., Zha, J., Jockel, J., Boise, L. H., Thompson, C. B., and Korsmeyer, S. J. (1995). Bad, a heterodimeric partner for Bcl-xL and Bcl-2, displaces Bax and promotes cell death. Cell, 80, 285–91CrossRef Google Scholar PubMed

Yang, J., Liu, X., Bhalla, K.et al. (1997). Prevention of apoptosis by bcl-2: release of cytochrome c from mitochondria blocked. Science, 275, 1129–32CrossRef Google Scholar PubMed

Yang, L., Matthews, R. T., Schulz, J. B.et al. (1998). 1-methyl-4-phenyl-1,2,3,6-tetrahydropyride neurotoxicity is attenuated in mice overexpressing Bcl-2. J. Neurosci., 18, 8145–52CrossRef Google Scholar PubMed

Yankner, B. A., Dawes, L. R., Fisher, S.et al. (1989). Neurotoxicity of a fragment of the amyloid precursor associated with Alzheimer's disease. Science, 245, 417–20CrossRef Google Scholar PubMed

Yoshio, H., Kong, Y.-Y., Yoshida, R.et al. (1998). Apaf1 is required for mitochondrial pathways of apoptosis and brain development. Cell, 94, 739–50CrossRef Google Scholar

Younkin, S. G. (1995). Evidence that A beta 42 is the real culprit in Alzheimer's disease. Ann. Neurol., 37, 287–8CrossRef Google Scholar PubMed

Yu, Z. X., Li, S. H., Evans, J., Pillarsetti, A., Li, H., and Li, X. J. (2003). Mutant huntingtin causes context – dependent neurodegeneration in mice with Huntington's disease. J. Neurosci., 23, 2193–202CrossRef Google Scholar PubMed

Yuan, J., Lipinski, M., and Degterev, A. (2003). Diversity in the mechanisms of neuronal cell death. Neuron, 40, 401–13CrossRef Google Scholar PubMed

Yue, Z., Horton, A., Bravin, M., DeJager, P. L., Selimi, F., and Heintz, N. (2002). A novel protein complex linking the δ2 glutamate receptor and autophagy: implications for neurodegeneration in Lurcher mice. Neuron, 35, 921–33CrossRef Google Scholar

Zha, J., Harada, H., Yang, E., Jockel, J., and Korsmeyer, S. J. (1996). Serine phosphorylation of death agonist Bad in response to survival factor results in binding to 14-3-3 not Bcl-xL. Cell, 87, 619–28CrossRef Google Scholar PubMed

Zhang, Y., McLaughlin, R., Goodyer, C., and LeBlanc, A. (2002). Selective cytotoxicity of intracellular amyloid β peptide1-42 through p53 and Bax in cultured primary human neurons. J. Cell Biol., 156, 519–29CrossRef Google Scholar PubMed

Zong, W.-X., Li, C., Hatzivassiliou, G.et al. (2003). Bax and Bak can localize to the endoplasmic reticulum to initiate apoptosis. J. Cell Biol., 162, 59–69CrossRef Google Scholar PubMed

Zou, H., Li, Y., Liu, X., and Wang, X. (1999). An Apaf-1-cytochrome c multimeric complex is a functional apoptosome that activates procaspase-9. J. Biol. Chem., 274, 11549–56CrossRef Google Scholar PubMed

Zuch, C. L., Nordstroem, V. K., Briedrick, L. A., Hoering, G. R., Granholm, A.-C., and Bickford, P. C. (2000). Time course of degenerative alterations in nigral dopaminergic neurons following a 6-hydroxydopamine lesion. J. Comp. Neurol., 427, 440–543.0.CO;2-7>CrossRef Google Scholar PubMed

Accessibility standard: Unknown

Accessibility compliance for the PDF of this book is currently unknown and may be updated in the future.