Oxidative stress and genetics in the pathogenesis of Parkinson's disease.
Parkinson's Disease (PD) is the second most common chronic neurodegenerative disease characterized by the progressive loss of dopamine neurons, leading to rigidity, slowness of movement, rest tremor, gait disturbances, and imbalance. Although there is effective symptomatic treatment for PD, there is no proven preventative or regenerative therapy. The etiology of this disorder remains unknown. Recent genetic studies have identified mutations in alpha-synuclein as a rare cause of autosomal dominant familial PD and mutations in parkin as a cause of autosomal recessive familial PD. The more common sporadic form of PD is thought to be due to oxidative stress and derangements in mitochondrial complex I activity. Understanding the mechanism by which familial linked mutations and oxidative stress cause PD has tremendous potential for unraveling the mechanisms of dopamine cell death in PD. In this article, we review recent advances in the understanding of the role of genetics and oxidative stress in the pathogenesis of PD.
Zhang
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Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21287, USA.
Dawson
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VL
Dawson
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D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D010300:Parkinson Disease / Q000235:genetics* / Q000473:pathology; D010302:Parkinson Disease, Secondary / Q000139:chemically induced; D051843:Synucleins; D051844:alpha-Synuclein
D015259:Dopamine Agents; D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; C496320:NOS1 protein, human; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D004298:Dopamine