Mechanisms of neurodegeneration in amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis (ALS) is the most common variant of motor neurone disease affecting adults that usually strikes during mid to late life. Its aetiology is still poorly understood, although a major breakthrough came with the discovery that mutations in the Cu/Zn superoxide dismutase (SOD1) gene affect approximately 20% of patients with familial ALS. Experiments using both transgenic mice and ALS tissues have been useful in delineating other genetic defects in ALS. However, because only a subset of cases can be attributed to one particular molecular defect (such as mutation of SOD1 or the gene encoding neurofilament H), the aetiology of ALS is likely to be multifactorial. This review discusses the major mechanisms of neurodegeneration in ALS, such as oxidative stress, glutaminergic excitotoxicity, damage to vital organelles, and aberrant protein aggregation.
Cluskey
S
S
Department of Medicine, University of Birmingham, Queen Elizabeth Hospital, Birmingham B15 2TH, UK.
Ramsden
D B
DB
D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D003300:Copper / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D023421:Models, Animal; D009154:Mutation; D009410:Nerve Degeneration; D016900:Neurofilament Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D018384:Oxidative Stress; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1
D016900:Neurofilament Proteins; C000606290:SOD1 protein, human; D018698:Glutamic Acid; D003300:Copper; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1