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 have developed antibodies that recognize specific advanced glycation end-products (anti-pentosidine and anti-pyrraline), protein modifications that are potentiated by oxidative stress in a process termed glycoxidation. We applied these antibodies immunocytochemically to affected regions in Parkinson disease and diffuse Lewy body disease brains. Additionally, we used antibodies to heme oxygenase-1, a putative marker of oxidative stress response. Immunoreactivity to pentosidine, pyrraline, and heme oxygenase-1 was seen in the substantia nigra of Parkinson disease and the neocortex of diffuse Lewy body disease. Heme oxygenase-1 was further demonstrated by immunoelectron microscopy in intimate association with filaments of cortical Lewy bodies. Immunolocalization of advanced glycation end-products and a marker of oxidative stress response induction provides evidence that glycoxidation and oxidative stress may be an important pathogenic factor in diseases characterized by Lewy body formation, and furthers the evidence that cytoskeletal proteins and their inclusions are susceptible to oxidative stress.
Castellani
R
R
Department of Pathology (Neuropathology), University of Maryland, Baltimore 21201-1595, USA.
Smith
M A
MA
Richey
P L
PL
Perry
G
G
D000368:Aged; D000369:Aged, 80 and over; D001120:Arginine / Q000031:analogs & derivatives / Q000032:analysis; D002540:Cerebral Cortex / Q000737:chemistry / Q000201:enzymology; D003432:Cross-Linking Reagents / Q000032:analysis; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006031:Glycosylation; D006419:Heme Oxygenase (Decyclizing) / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D008125:Locus Coeruleus / Q000737:chemistry / Q000201:enzymology; D008239:Lysine / Q000031:analogs & derivatives / Q000032:analysis; D016253:Microscopy, Immunoelectron; D008875:Middle Aged; D009474:Neurons / Q000737:chemistry / Q000201:enzymology / Q000648:ultrastructure; D009646:Norleucine / Q000031:analogs & derivatives / Q000032:analysis; D018384:Oxidative Stress / Q000502:physiology*; D010300:Parkinson Disease / Q000378:metabolism* / Q000503:physiopathology; D011758:Pyrroles / Q000032:analysis; D013378:Substantia Nigra / Q000737:chemistry / Q000201:enzymology
D003432:Cross-Linking Reagents; D017127:Glycation End Products, Advanced; D011758:Pyrroles; C059571:2-formyl-5-(hydroxymethyl)pyrrole-1-norleucine; D009646:Norleucine; D001120:Arginine; C062187:pentosidine; D006419:Heme Oxygenase (Decyclizing); D008239:Lysine