GLYCOXIDATION AND OXIDATIVE STRESS IN PARKINSON DISEASE AND DIFFUSE LEWY BODY DISEASE

Oxidative stress is well accepted as an important pathogenic factor in Parkinson disease, based largely on indirect evidence. Recently, we h ave developed antibodies that recognize specific advanced glycation en d-products (anti-pentosidine and anti-pyrraline), protein modification s that are potentiated by oxidative stress in a process termed glycoxi dation. We applied these antibodies immunocytochemically to affected r egions in Parkinson disease and diffuse Lewy body disease brains. Addi tionally, we used antibodies to heme oxygenase-l, a putative marker of oxidative stress response. Immunoreactivity to pentosidine, pyrraline , and heme oxygenase-l was seen in the substantia nigra of Parkinson d isease and the neocortex of diffuse Lewy body disease. Heme oxygenase- 1 was further demonstrated by immunoelectron microscopy in intimate as sociation with filaments of cortical Lewy bodies. Immunolocalization o f advanced glycation end-products and a marker of oxidative stress res ponse induction provides evidence that glycoxidation and oxidative str ess may be an important pathogenic factor in diseases characterized by Lewy body formation, and furthers the evidence that cytoskeletal prot eins and their inclusions are susceptible to oxidative stress.