Review: The role of mitochondria in the pathogenesis of amyotrophic lateral sclerosis

L. M. Duffy, A. L. Chapman, P. J. Shaw and A. J. Grierson (2011) Neuropathology and Applied Neurobiology37, 336–352 The role of mitochondria in the pathogenesis of amyotrophic lateral sclerosis Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by loss of upper and lower motor neurones leading to muscle weakness and paralysis. Despite recent advances in the genetics of ALS, the mechanisms underlying motor neurone degeneration are not fully understood. Mitochondria are known to be involved in the pathogenesis of ALS, principally through mitochondrial dysfunction, the generation of free radicals, and impaired calcium handling in ALS patients and models of disease. However, recent studies have highlighted the potential importance of altered mitochondrial morphology and defective axonal transport of mitochondria in ALS. Here, we review the evidence for mitochondrial involvement in ALS and discuss potential therapeutic strategies targeting mitochondria.