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Molecular and cellular pathways of neurodegeneration in motor neurone disease

Correspondence to:
Correspondence to:
Professor Pamela J Shaw
Academic Neurology Unit, E Floor, School of Medicine and Biomedical Sciences, Beech Hill Road, Sheffield S10 2RX; Pamela.Shaw{at}sheffield.ac.uk

ABSTRACT
The process of neuronal degeneration in motor neurone disease is complex. Several genetic alterations may be involved in motor neurone injury in familial amyotrophic lateral sclerosis, less is known about the genetic and environmental factors involved in the commoner sporadic form of the disease. Most is known about the mechanisms of motor neurone degeneration in the subtype of disease caused by SOD1 mutations, but even here there appears to be a complex interplay between multiple pathogenic processes including oxidative stress, protein aggregation, mitochondrial dysfunction excitotoxicity, and impaired axonal transport. There is new evidence that non-neuronal cells in the vicinity of motor neurones may contribute to neuronal injury. The final demise of motor neurones is likely to involve a programmed cell death pathway resembling apoptosis.

Abbreviations: ALS, amyotrophic lateral sclerosis; CNTF, ciliary neurotrophic factor; GEF, guanine nucleotide exchange factor; HRE, hypoxia response element; MND, motor neurone disease; VAPB, vesicle associated membrane protein/synaptobrevin associated membrane protein; VEGF, vascular endothelial growth factor

Keywords: motor neurone disease; neurodegeneration

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