PMC:3346999 / 4294-6416 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/3346999","sourcedb":"PMC","sourceid":"3346999","source_url":"http://www.ncbi.nlm.nih.gov/pmc/3346999","text":"2. Reactive Oxygen Species and PD\nPD, the second most major neurodegenerative disease after AD, is a pathological condition characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta and loss of striatal dopamine content [16, 17]. Although several pathogenic hypotheses have been proposed for PD, oxidative stress via the generation of ROS is considered one of the major contributors. Evidence for the role of ROS was first observed in human PD brains showing mitochondrial dysfunction and oxidative damage in the degenerating areas including the substantia nigra [18, 19]. Dopamine is a relatively unstable molecule subject to hydroxyl radical attack that can induce ROS damage both from within and outside the cell [20]. ROS generated from mitochondrial and/or extramitochondrial sources appear to be the main contributor of oxidative stress-mediated neurodegeneration in PD models [16, 21–27]. Importantly, generation of ROS from toxicity induced by accumulation of MPP+ in the inner mitochondrial membrane, disruption of complex I in the electron transport chain, and interaction of MPP+ with iron stores within the pigmented substantia nigra cells are the known sources of oxidative stress [28–31].\nIncreasing evidence indicates that inflammatory-activated microglia and astrocytes are considered to be a consequence of neuronal cell death in AD, PD, HD ALS, and multiple sclerosis [32–36]. Activated microglia highly expresses several enzymes including iNOS, NADPH oxidase, COX-2, and myeloperoxidase responsible for inflammatory processes mediated by oxidative stress. These enzymes contribute to the pathogenesis of various neurodegenerative diseases [13, 37–39]. ROS-generating multimeric enzymes are indispensable for protecting the host against infections and injuries. Inappropriate activation of these enzymes may be harmful in noninfectious neurodegenerative disorders [40, 41]. Thus, the discovery of various novel agents that inhibit the activation of these enzymes may prove to be a therapeutic strategy in ameliorating various neurodegenerative diseases including 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