Free radicals in Parkinson's disease.
Although there are a number of hypotheses to explain the pathobiochemistry of Parkinson's disease (PD), the one on oxidative stress (OS) has gained major interest. The evidence for OS participation as a cause of PD can be summarized as follows: 1) OS is involved in physiological aging, 2) there is ample evidence that OS is significantly enhanced in PD compared to age-matched healthy persons, 3) OS is an early feature of PD because OS-dependent aggregation of proteins in the form of advanced glycation end products can be imaged in Lewy bodies at a time in a person's life, when no phenotype of a neurodegenerative disorder is evident, 4) Experimental models of PD show OS and degeneration of dopaminergic neurons. The toxin-induced neurodegeneration can be blocked by antioxidants, and 5) Activated microglia, known to release free radicals and inflammatory cytokines, are present in brains of Parkinsonian patients. In conclusion, a great body of evidence points to the view that OS is a major component underlying the pathobiochemistry of PD. Together a genetic disposition and endogenous/exogenous toxic events of various origins result in a synergistic cascade of toxicity which leads to dysfunction and finally to cell death of dopaminergic neurons. Again, OS plays a significant role in generating cell death signals including apoptosis.
Koutsilieri
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Clinical Neurochemistry and NPF Center of Excellence Research Laboratory, Department of Psychiatry and Psychotherapy, Julius-Maximilians-University, Fuechsleinstr. 15, 97080 Wuerzburg, Germany. eleni.koutsilieri@mail.uni-wuerzburg.de
Scheller
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C
Grünblatt
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E
Nara
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K
Li
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J
Riederer
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P
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D004195:Disease Models, Animal; D005609:Free Radicals / Q000378:metabolism*; D006801:Humans; D017628:Microglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000209:etiology* / Q000378:metabolism*
D015415:Biomarkers; D005609:Free Radicals