Amyotrophic lateral sclerosis associated with mutations in superoxide dismutase: a putative mechanism of degeneration

Amyotrophic lateral sclerosis (ALS) is a devastating neurologic disease tha t rapidly progresses from mild motor symptoms to severe motor paralysis and premature death. Until recently, there were few substantive studies conduc ted on the pathogenesis of the disease. With the genetic linkage of mutatio ns in the superoxide dismutase (SOD-1) gene with familial ALS patients, new avenues for study have become available including transgenic mice and cult ure models. Although not yet providing a complete picture of the disease me chanism, studies utilizing these model systems have greatly advanced our un derstanding of the mechanism of degeneration and should eventually lead to putative therapeutic agents. In this review, we will present the important findings from these model systems, provide a framework in which to evaluate these findings, and speculate on the mechanism of degeneration initiated b y the mutations in SOD-1. (C) 1994 Elsevier Science B.V. All rights reserve d.