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Progress in Clinical Neurosciences: The Evidence for ALS as a Multisystems Disorder of Limited Phenotypic Expression

Published online by Cambridge University Press:  02 December 2014

Michael J. Strong*
Affiliation:
Department of Clinical Neurological Sciences, The University of Western Ontario, London, Ontario, Canada
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Abstract

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Traditionally, amyotrophic lateral sclerosis (ALS) is considered to be a unique neurodegeneration disorder in which motor neurons are selectively vulnerable to a single disease process. Our current understanding of ALS, however, suggests that this is far too limited an approach. While motor neuron degeneration remains the central component to this process, there is considerable phenotypic variability including broad ranges in survivorship and the presence or absence of cognitive impairment. The number of familial variants of ALS for which unique genetic linkage has been identified is increasing, attesting further to the biological heterogeneity of the disorder. At the cellular level, derangements in cytoskeletal protein and glutamate metabolism, mitochondrial function, and in glial interactions are clearly evident. When considered in this fashion, ALS can be justifiably considered a disorder of multiple biological processes sharing in common the degeneration of motor neurons.

Résumé:

RÉSUMÉ:

Observations indiquant que la SLA est une maladie multisystémique à expression phénotypique limitée. Traditionnellement, la SLA était considérée comme une maladie neurodégénérative dans laquelle les motoneurones sont vulnérables de façon sélective à un processus pathologique unique. Notre compréhension actuelle de la SLA suggère cependant que cette approche est beaucoup trop étroite. Bien que la dégénérescence des motoneurones demeure l'élément central de ce processus, il existe une variabilité phénotypique considérable particulièrement quant à la survie et à la présence ou à l'absence de déficit cognitif. Le nombre de variantes familiales de la SLA pour lesquelles une liaison génétique a été identifiée augmente, attestant de l'hétérogénéité biologique de la maladie. Au niveau cellulaire, il existe des perturbations de la protéine cytosquelettique et du métabolisme du glutamate, de la fonction mitochondriale et des interactions gliales. Quand on regarde la SLA sous cet aspect, on peut à juste titre la considérer comme une maladie due à des processus biologiques multiples ayant en commun la dégénérescence de motoneurones.

Type
Review Article
Copyright
Copyright © The Canadian Journal of Neurological 2001

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