RT Journal Article SR Electronic T1 Mechanisms of neurodegeneration in amyotrophic lateral sclerosis JF Molecular Pathology JO Mol Pathol FD BMJ Publishing Group Ltd and Association of Clinical Pathologists SP 386 OP 392 DO 10.1136/mp.54.6.386 VO 54 IS 6 A1 S Cluskey A1 D B Ramsden YR 2001 UL http://mp.bmj.com/content/54/6/386.abstract AB 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.