title: Neurodegeneration and inflammation in Parkinson's disease.
abstract: Parkinson's disease (PD) is characterized by the progressive degeneration of dopamine (DA) neurons of the substantia nigra pars compacta (SNpc) accompanied by a buildup of proteinaceous aggregates termed Lewy bodies (LB). In addition to protein aggregation and the loss of DA signaling, PD is also characterized by an active immune response. T-cell infiltration accompanies activated microglial and astrocytic accumulation in and around the SNpc. Although potentially beneficial, microglial activation is most likely responsible for furthering disease pathology and DA neuron degeneration through the release of harmful substances such as pro-inflammatory cytokines, reactive oxidative species and reactive nitrogen species. Activation of the NF-κB death pathway has been shown to occur following microglial activation related release of Cox-2, IL-1β, and Toll-like receptor activation, resulting in increased degeneration of DA neurons of the SNpc. Blockade of microglial activation can lead to DA neuron protection in animal models of PD; however, clinical application of anti-inflammatory drugs has not yielded similar benefits. Future therapeutic designs must take into account the multifactorial nature of PD, including the varied roles of the adaptive and innate immune responses.
authors.affiliation: Department of Neurology, Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.
authors.forename: Sudarshan
authors.initials: S
authors.lastname: Phani
authors.forename: John D
authors.initials: JD
authors.lastname: Loike
authors.forename: Serge
authors.initials: S
authors.lastname: Przedborski
mesh_terms: D000818:Animals; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*