Neurofilaments, free radicals, excitotoxins, and amyotrophic lateral sclerosis

There is increasing evidence implicating abnormalities of neurofilament function in the pathogenesis of amyotrophic lateral sclerosis (ALS). The observation that the P2 blood protein phenotype is overrepresented in patients with ALS is potentially important, but needs confirmation. It should be shown that this segregation is selective for ALS. If it is, the implications outlined in Meyer's hypothesis will need to be explored, bearing in mind that much of the evidence implicating excitotoxins, free radicals, and neurofilaments in familial and sporadic ALS is still circumstantial. Thus the identification of candidate genes, the pursuit of large segregation studies, and identification of specific point mutations, remain key goals in ALS research.