Superoxide Dismutase and Oxidative Stress in Amyotrophic Lateral Sclerosis

Abstract

OVERVIEW OF AMYOTROPHIC LATERAL SCLEROSIS
Amyotrophic lateral sclerosis (ALS) is an adult-onset, degenerative disorder of motor neurons in the motor cortex, spinal cord, and brain stem. It is characterized by focal onset of paralysis which spreads relentlessly, often in a pattern suggesting involvement of contiguously located motor neurons within the spinal cord. Respiratory paralysis leads to death, usually within 3–5 years. There are no definitive treatments for this disease. The prevalence of ALS is about 5/100,000 and its incidence is 0.4–1.8/100,000 (Fosgren et al. 1983; Mulder et al. 1986). The central pathological finding in ALS is degeneration and loss of large motor neurons in the cerebral cortex, brain stem, and spinal cord (Brownell et al. 1970). There is a reduction in numbers of large myelinated axons, axonal degeneration, and distal axonal atrophy in peripheral nerves (Brownell et al. 1970; Tanaka et al. 1984). Rarely, one encounters subclinical pathology of non-motor neurons and tracts including the posterior columns, Clarke’s column, and the spinocerebellar tracts, particularly in familial forms of the disease (Brownell et al. 1970; Tanaka et al. 1984). Some motor neurons show hyaline inclusions resembling Lowey bodies (Takahasi et al. 1972) and accumulations of ubiquitin-positive material (Hirano 1991). Ten to fifteen percent of ALS cases are familial (FALS) with autosomal dominant inheritance (Horton et al. 1976; Mulder et al. 1986).

GENETIC INVESTIGATIONS AND THE FREE RADICAL HYPOTHESIS IN ALS
A multi-center, collaborative study identified a locus for FALS on chromosome 21q (Siddique et al. 1991) and subsequently described...