Role of oxidative damage in protein aggregation associated with Parkinson's disease and related disorders.
Parkinson's disease, the most common movement disorder, is characterized by the loss of brainstem neurons, specifically dopaminergic neurons in the substantia nigra, as well as the accumulation of neuronal cytoplasmic filamentous proteinaceous inclusions comprised of polymerized alpha-synuclein. It was reported recently that alpha-synuclein can induce the formation of filamentous tau inclusions, which are characteristic of disorders like Alzheimer's disease and Lewy body variant of Alzheimer's disease, suggesting that a similar mechanism may exist between alpha-synuclein fibrillogenesis and tau polymerization. Pathological brain inclusions comprised of alpha-synuclein or tau proteins are associated with a spectrum of neurodegenerative disorders, and oxidative and nitrative injury has been implicated in all of these diseases. However, the role of oxidative damage in alpha-synuclein and tau polymerization and pathological inclusion formation is complex. Differences in the level, type, and temporal sequence of the oxidative alterations appear to result in both inhibitory and stimulatory effects on the fibrillogenesis of these proteins.
Norris
Erin H
EH
Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Giasson
Benoit I
BI
D000818:Animals; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism; D016631:Lewy Bodies / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009566:Nitrates / Q000378:metabolism; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology*; D051843:Synucleins; D051844:alpha-Synuclein
D009419:Nerve Tissue Proteins; D009566:Nitrates; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein