OXIDATIVE STRESS, AGE-RELATED NEURODEGENERATION, AND THE POTENTIAL FOR NEUROTROPHIC TREATMENT

Amyotrophic lateral sclerosis, Parkinson's disease, and Alzheimer's di sease are major human neurodegenerative disorders, the etiologies for which remain unknown. Although a unique subset of neurons is particula rly affected in each of the three diseases, they have several intrigui ng overlapping similarities. Evidence is reviewed supporting the hypot hesis that these diseases result from an inability to protect against accumulated damage by free radicals due to oxidative stress. If oxidat ive stress underlies or exacerbates the etiology of these diseases, th en agents that effectively attenuate brain tissue lipid peroxidation o r otherwise limit free radical damage may hold promise for the treatme nt of these neurodegenerative diseases. Although antioxidant chemical supplementation may provide effective therapy, the most effective ther apy for neurodegenerative diseases may be treatment with specific neur otrophic, survival-promoting proteins, For example, brain-derived neur otrophic factor promotes survival of spinal motor neurons and mesencep halic dopaminergic neurons. One mechanism through which these proteins may exert their protection may be by stimulating endogenous defenses against oxidative stress and damage by free radicals. This hypothesis is being tested in several laboratories and provides exciting directio n both for basic neurobiological research and therapeutic drug discove ry.