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Aggregated alpha-synuclein activates microglia: a process leading to disease progression in Parkinson's disease.
FASEB J. 2005 Apr; 19(6):533-42.FJ

Abstract

A growing body of evidence indicates that an inflammatory process in the substantia nigra, characterized by activation of resident microglia, likely either initiates or aggravates nigral neurodegeneration in Parkinson's disease (PD). To study the mechanisms by which nigral microglia are activated in PD, the potential role of alpha-synuclein (a major component of Lewy bodies that can cause neurodegeneration when aggregated) in microglial activation was investigated. The results demonstrated that in a primary mesencephalic neuron-glia culture system, extracellular aggregated human alpha-synuclein indeed activated microglia; microglial activation enhanced dopaminergic neurodegeneration induced by aggregated alpha-synuclein. Furthermore, microglial enhancement of alpha-synuclein-mediated neurotoxicity depended on phagocytosis of alpha-synuclein and activation of NADPH oxidase with production of reactive oxygen species. These results suggest that nigral neuronal damage, regardless of etiology, may release aggregated alpha-synuclein into substantia nigra, which activates microglia with production of proinflammatory mediators, thereby leading to persistent and progressive nigral neurodegeneration in PD. Finally, NADPH oxidase could be an ideal target for potential pharmaceutical intervention, given that it plays a critical role in alpha-synuclein-mediated microglial activation and associated neurotoxicity.

Authors+Show Affiliations

Neuropharmacology Section, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences/National Institutes of Health, Research Triangle Park, North Carolina, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15791003

Citation

Zhang, Wei, et al. "Aggregated Alpha-synuclein Activates Microglia: a Process Leading to Disease Progression in Parkinson's Disease." FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, vol. 19, no. 6, 2005, pp. 533-42.
Zhang W, Wang T, Pei Z, et al. Aggregated alpha-synuclein activates microglia: a process leading to disease progression in Parkinson's disease. FASEB J. 2005;19(6):533-42.
Zhang, W., Wang, T., Pei, Z., Miller, D. S., Wu, X., Block, M. L., Wilson, B., Zhang, W., Zhou, Y., Hong, J. S., & Zhang, J. (2005). Aggregated alpha-synuclein activates microglia: a process leading to disease progression in Parkinson's disease. FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, 19(6), 533-42.
Zhang W, et al. Aggregated Alpha-synuclein Activates Microglia: a Process Leading to Disease Progression in Parkinson's Disease. FASEB J. 2005;19(6):533-42. PubMed PMID: 15791003.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Aggregated alpha-synuclein activates microglia: a process leading to disease progression in Parkinson's disease. AU - Zhang,Wei, AU - Wang,Tongguang, AU - Pei,Zhong, AU - Miller,David S, AU - Wu,Xuefei, AU - Block,Michelle L, AU - Wilson,Belinda, AU - Zhang,Wanqin, AU - Zhou,Yong, AU - Hong,Jau-Shyong, AU - Zhang,Jing, PY - 2005/3/26/pubmed PY - 2005/12/15/medline PY - 2005/3/26/entrez SP - 533 EP - 42 JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology JO - FASEB J VL - 19 IS - 6 N2 - A growing body of evidence indicates that an inflammatory process in the substantia nigra, characterized by activation of resident microglia, likely either initiates or aggravates nigral neurodegeneration in Parkinson's disease (PD). To study the mechanisms by which nigral microglia are activated in PD, the potential role of alpha-synuclein (a major component of Lewy bodies that can cause neurodegeneration when aggregated) in microglial activation was investigated. The results demonstrated that in a primary mesencephalic neuron-glia culture system, extracellular aggregated human alpha-synuclein indeed activated microglia; microglial activation enhanced dopaminergic neurodegeneration induced by aggregated alpha-synuclein. Furthermore, microglial enhancement of alpha-synuclein-mediated neurotoxicity depended on phagocytosis of alpha-synuclein and activation of NADPH oxidase with production of reactive oxygen species. These results suggest that nigral neuronal damage, regardless of etiology, may release aggregated alpha-synuclein into substantia nigra, which activates microglia with production of proinflammatory mediators, thereby leading to persistent and progressive nigral neurodegeneration in PD. Finally, NADPH oxidase could be an ideal target for potential pharmaceutical intervention, given that it plays a critical role in alpha-synuclein-mediated microglial activation and associated neurotoxicity. SN - 1530-6860 UR - https://www.unboundmedicine.com/medline/citation/15791003/Aggregated_alpha_synuclein_activates_microglia:_a_process_leading_to_disease_progression_in_Parkinson's_disease_ L2 - https://doi.org/10.1096/fj.04-2751com DB - PRIME DP - Unbound Medicine ER -