Environmental Toxicity and ALS: Novel Insights from an Animal Model of ALS-PDC

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and incurable neurological disorder which typically kills its victims within three to five years of clinical diagnosis. ALS is characterized pathologically by the loss of upper and lower motor neurons in the CNS accompanied by muscle wasting and the loss of motor function. Over 90% of cases are sporadic ALS (SALS) with no clear etiology (1,2). Of the familial cases of ALS, approximately 20% appear to arise due to a toxic gain of function mutation in genes coding for the antioxidant enzyme superoxide dismutase (SOD) (1). Five percent of people with SALS also have Cu/Zn superoxide dismutase (SOD1)mutations (3). A second mutation in a gene coding for a protein of unknown function, ‘‘alsin,’’ produces a rare juvenile variant form of the disease (ALS2) (4).