title: Oxidative damage to macromolecules in human Parkinson disease and the rotenone model.
abstract: Parkinson disease (PD), the most common neurodegenerative movement disorder, is associated with selective degeneration of nigrostriatal dopamine neurons. Although the underlying mechanisms contributing to neurodegeneration in PD seem to be multifactorial, mitochondrial impairment and oxidative stress are widely considered to be central to many forms of the disease. Whether oxidative stress is a cause or a consequence of dopaminergic death, there is substantial evidence for oxidative stress both in human PD patients and in animal models of PD, especially using rotenone, a complex I inhibitor. There are many indices of oxidative stress, but this review covers the recent evidence for oxidative damage to nucleic acids, lipids, and proteins in both the brain and the peripheral tissues in human PD and in the rotenone model. Limitations of the existing literature and future perspectives are discussed. Understanding how each particular macromolecule is damaged by oxidative stress and the interplay of secondary damage to other biomolecules may help us design better targets for the treatment of PD.
authors: Pittsburgh Institute for Neurodegenerative Diseases, Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15260, USA.
authors: Laurie H
authors: LH
authors: Sanders
authors: Pittsburgh Institute for Neurodegenerative Diseases, Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15260, USA. Electronic address: jgreena@pitt.edu.
authors: J
authors: J
authors: Timothy Greenamyre
mesh_terms: D000818:Animals; D004249:DNA Damage; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D050356:Lipid Metabolism; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D011506:Proteins / Q000378:metabolism; D012402:Rotenone / Q000506:poisoning
chemical_list: D011506:Proteins; D012402:Rotenone
keywords: 4-hydroxy-2-nonenal; ATP; CSF; DA; ETC; Free radicals; HNE; L-DOPA; LB; Lewy body; MDA; Macromolecules; O(2)(−); OH(•); Oxidative damage; PD; PUFA; Parkinson disease; ROS; Rotenone; SN; VTA; adenosine-5′-triphosphate; cerebrospinal fluid; dopamine; electron transport chain; hydroxyl radical; levodopa, l-3,4-dihydroxyphenylalanine; malondialdehyde; mitochondrial DNA; mtDNA; polyunsaturated fatty acid; reactive oxygen species; substantia nigra pars compacta; superoxide; ventral tegmental area