Microglia, major player in the brain inflammation: their roles in the pathogenesis of Parkinson's disease.
Inflammation, a self-defensive reaction against various pathogenic stimuli, may become harmful self-damaging process. Increasing evidence has linked chronic inflammation to a number of neurodegenerative disorders including Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis. In the central nervous system, microglia, the resident innate immune cells play major role in the inflammatory process. Although they form the first line of defense for the neural parenchyma, uncontrolled activation of microglia may directly toxic to neurons by releasing various substances such as inflammatory cytokines (IL-1beta, TNF-alpha, IL-6), NO, PGE(2), and superoxide. Moreover, our recent study demonstrated that activated microglia phagocytose not only damaged cell debris but also neighboring intact cells. It further supports their active participation in self-perpetuating neuronal damaging cycles. In the following review, we discuss microglial responses to damaging neurons, known activators released from injured neurons and how microglia cause neuronal degeneration. In the last part, microglial activation and their role in PD are discussed in depth.
Kim
Yoon Seong
YS
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, NY 10021, USA. yok2001@med.cornell.edu
Joh
Tong H
TH
D015526:AIDS Dementia Complex / Q000209:etiology; D000544:Alzheimer Disease / Q000209:etiology; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004660:Encephalitis / Q000209:etiology* / Q000276:immunology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D019278:Matrix Metalloproteinase 3; D008543:Melanins / Q000502:physiology; D045726:Metalloproteases / Q000502:physiology; D017628:Microglia / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D009103:Multiple Sclerosis / Q000209:etiology; D010300:Parkinson Disease / Q000209:etiology* / Q000276:immunology; D015398:Signal Transduction; D051844:alpha-Synuclein / Q000502:physiology
D016207:Cytokines; D018836:Inflammation Mediators; D008543:Melanins; D051844:alpha-Synuclein; C014121:neuromelanin; D045726:Metalloproteases; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3