4 results
Contributors
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- By Sofya Abazyan, Saskia S. Arndt, Jonathon C. Arnold, Sandra Beeské, Odd-Geir Berge, Valerie J. Bolivar, David Borchelt, Marie-Françoise Chesselet, Yoon H. Cho, Angelo Contarino, John C. Crabbe, Wim E. Crusio, Bianca De Filippis, Mara Dierssen, Stephanie C. Dulawa, Emily C. Eastwood, Haim Einat, Raul R. Gainetdinov, David Gordon, Guy Griebel, F. Scott Hall, John H. Harkness, Christopher Janus, Zhengping Jia, Nirit Kara, Tim Karl, Martien J. H. Kas, Federica Klaus, Robert Lalonde, Glenda Lassi, Giovanni Laviola, Iddo Magen, Stephen C. Maxson, Douglas Ashley Monks, Rebecca E. Nordquist, Lucy R. Osborne, Tamara J. Phillips, Alisdair R. Philp, Marina R. Picciotto, Susanna Pietropaolo, Mikhail V. Pletnikov, Christopher R. Pryce, James L. Resnick, Laura Ricceri, Frans Sluyter, Emily Y. Smith, Ichiro Sora, Tatyana D. Sotnikova, Rebecca C. Steiner, Ortrud K. Steinlein, Catherine Strazielle, Enejda Subashi, Ashlyn Swift-Gallant, Aki Takahashi, Kevin Talbot, Stewart Thompson, Valter Tucci, F. Josef van der Staay, Gertjan van Dijk, Nancy S. Woehrle
- Edited by Susanna Pietropaolo, Centre National de la Recherche Scientifique (CNRS), Paris, Frans Sluyter, University of Portsmouth, Wim E. Crusio, Centre National de la Recherche Scientifique (CNRS), Paris
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- Book:
- Behavioral Genetics of the Mouse
- Published online:
- 05 October 2014
- Print publication:
- 25 September 2014, pp ix-xii
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15 - Selected genetically engineered models relevant to human neurodegenerative disease
- from Part I - Basic aspects of neurodegeneration
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- By Donald L. Price, Department of Pathology, Division of Neuropathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA, David R. Borchelt, Department of Neurology, Division of Neuropathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA, Michael K. Lee, Department of Neurscience, Division of Neuropathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA, Philip C. Wong, Division of Neuropathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
- M. Flint Beal, Cornell University, New York, Anthony E. Lang, University of Toronto, Albert C. Ludolph, Universität Ulm, Germany
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- Book:
- Neurodegenerative Diseases
- Published online:
- 04 August 2010
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- 02 June 2005, pp 176-195
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Summary
Introduction
This review on selected neurodegenerative diseases, including Alzheimer's disease, amyotrophic lateral sclerosis (ALS), and Parkinson's disease, and frontotemporal dementia with Parkinsonism (FTD-P), focuses on the ways by which genetically engineered models have clarified the mechanisms of these disorders and have identified new targets for therapy, and been used to test new treatment strategies. These neurodegenerative diseases are some of the most challenging diseases in medicine because of their general prevalence, cost, lack of mechanism-based treatments, and impact on individuals and caregivers (Lipp & Wolfer, 1998; Wong et al., 2002). The classical clinical phenotypes are, for the most part, quite distinct and reflect the dysfunction and death of specific populations of neurons. These brain lesions are characterized by the presence of intracellular or extracellular peptides/aggregates, which appear to be critical contributors to neurotoxicity, partially damaging to synapses. Genetic risk factors influence these age-associated, chronic illnesses. In rare instances, cases are inherited in Mendelian fashion (usually as autosomal dominants). Susceptibility genes, environmental risk factors, or other influences remain to be defined. Information from genetics has allowed investigators to express or to target genes in efforts to model these diseases and to study the (Armstrong et al., 1996) molecular participants critical in pathogenic pathways. This body of research is the principal topic of this review.
In this review, we emphasize the value of genetically engineered mouse models for studies of mechanisms and for experimental therapeutics, but we also briefly describe the extraordinary utility of non-mammalian genetic models.
24 - Transgenic mouse models of neurodegenerative disease
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- By David R. Borchelt, Departments of Pathology and Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA, Joanna Jankowsky, Departments of Pathology and Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA, Alena Savonenko, Departments of Pathology and Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA, Gabriele Schilling, Departments of Pathology and Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA, Jiou Wang, Departments of Pathology and Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA, Guilian Xu, Departments of Pathology and Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA
- Edited by Margaret M. Esiri, University of Oxford, Virginia M. -Y. Lee, University of Pennsylvania School of Medicine, John Q. Trojanowski, University of Pennsylvania School of Medicine
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- Book:
- The Neuropathology of Dementia
- Published online:
- 12 October 2009
- Print publication:
- 22 July 2004, pp 533-557
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Summary
The neurodegenerative diseases are an extraordinary challenge for science and medicine due to the grave nature of these illnesses, their prevalence, and their impact on individuals and caregivers. The most prevalent of these age-associated, chronic, illnesses include Alzheimer's disease (AD) and Parkinson's disease (PD); other examples include the prion disorders, amyotrophic lateral sclerosis, and the trinucleotide (CAG) repeat diseases. All of these diseases are characterized by well-defined clinical syndromes with progressive courses; evidence of dysfunction/death of specific populations of neurons; specific pathological and biochemical abnormalities; and the presence of intra- or extracellular protein aggregates (for review see Price et al., 1998). At present, there are treatments available that will ameliorate some of the symptoms, but none of these significantly alter the course of disease.
With the exception of the CAG repeat disorders, most cases of neurodegenerative disease arise from unknown aetiologies. However, a very small subset of cases are inherited, usually in an autosomal dominant fashion, and the identification of mutations in specific genes for some of these disorders has provided new opportunities to investigate the molecular participants in disease processes and to explore pathogenic mechanisms in model systems. Perhaps the greatest use of genetically engineered models has been to allow investigators to assess the in vitro and in vivo consequences of mutations in, or deletions of, genes implicated in neurodegenerative disorders. Knocking-out or over-expressing the products of genes that influence the pathways leading to disease has proved to be an extremely valuable strategy for examining some of the mechanisms and potential therapeutic targeting.
115 - Genetically engineered models of neurodegenerative diseases
- from PART XVI - DEGENERATIVE DISORDERS
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- By Philip C. Wong, The Johns Hopkins University School of Medicine, Baltimore, MD, USA, Huaibin Cai, The Johns Hopkins University School of Medicine, Baltimore, MD, USA, David R. Borchelt, The Johns Hopkins University School of Medicine, Baltimore, MD, USA, Donald L. Price, Neuroscience, and the Division of Neuropathology,
- Edited by Arthur K. Asbury, University of Pennsylvania School of Medicine, Guy M. McKhann, The Johns Hopkins University School of Medicine, W. Ian McDonald, University College London, Peter J. Goadsby, University College London, Justin C. McArthur, The Johns Hopkins University School of Medicine
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- Book:
- Diseases of the Nervous System
- Published online:
- 05 August 2016
- Print publication:
- 11 November 2002, pp 1841-1862
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