机构：[1]Neuropharmacology Section, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences/National Institutes of Health, Research Triangle Park, North Carolina[2]Department of Neurology, Beijing Tian Tan Hospital, Capital Medical University, Beijing, China[3]Intracellular Regulation Section, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences/National Institutes of Health, Research Triangle Park, North Carolina[4]Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, BC, Canada[5]Department of Neurology, Xuanwu Hospital, Capital University of Medical Sciences, Beijing, China神经内科首都医科大学宣武医院[6]Department of Physiology, Dalian Medical University, Dalian, China[7]Department of Pathology, University of Washington, Seattle, Washington
alpha-Synuclein, a gene whose mutations, duplication, and trip lication has been linked to autosomal dominant familial Parkinson's disease (fPD), appears to play a central role in the pathogenesis of sporadic PD (sPD) as well. Enhancement of neurodegeneration induced by mutant alpha-synuclein has been attributed to date largely to faster formation of alpha-synuclein aggregates in neurons. Recently, we reported that microglial activation enhances wild type (WT) alpha-synuclein-elicited dopaminergic neurodegeneration. In the present study, using a primary mesencephalic culture system, we tested whether mutated alpha-synuclein could activate microglia more powerfully than WT alpha-synuclein, thereby contributing to the accelerated neurodegeneration observed in fPD. The results showed that alpha-synuclein with the A30P or A53T mutations caused greater microglial activation than WT alpha-synuclein. Furthermore, the extent of microglial activation paralleled the degree of dopaminergic neurotoxicity induced by WT and mutant alpha-synuclein. Mutant alpha-synuclein also induced greater production of reactive oxygen species than WT alpha-synuclein by NADPH oxidase (PHOX), and PHOX activation was linked to direct activation of macrophage antigen-1 (Mac-1) receptor, rather than alpha-synuclein internalization via scavenger receptors. These results have, for the first time, demonstrated that microglia are also critical in enhanced neurotoxicity induced by mutant alpha-synuclein. (C) 2007 Wiley-Liss, Inc.
基金：
Intramural grants from NIH/NIEHS; Extramural grants: R01AG025327, R01ES012703.
第一作者机构：[1]Neuropharmacology Section, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences/National Institutes of Health, Research Triangle Park, North Carolina[2]Department of Neurology, Beijing Tian Tan Hospital, Capital Medical University, Beijing, China
通讯作者：
通讯机构：[*]Division of Neuropathology, Harborview Medical Center, University of Washington School of Medicine, Box 359635, 325 9th Avenue, Seattle, WA 98104-2499, USA
推荐引用方式(GB/T 7714)：
WEI ZHANG ,SHANNON DALLAS ,DAN ZHANG ,et al.Microglial PHOX and Mac-1 are essential to the enhanced dopaminergic neurodegeneration elicited by A30P and A53T mutant alpha-synuclein[J].GLIA.2007,55(11):1178-1188.doi:10.1002/glia.20532.
APA：
WEI ZHANG,,SHANNON DALLAS,,DAN ZHANG,,JIAN-PING GUO,,HAO PANG,...&JING ZHANG.(2007).Microglial PHOX and Mac-1 are essential to the enhanced dopaminergic neurodegeneration elicited by A30P and A53T mutant alpha-synuclein.GLIA,55,(11)
MLA：
WEI ZHANG,,et al."Microglial PHOX and Mac-1 are essential to the enhanced dopaminergic neurodegeneration elicited by A30P and A53T mutant alpha-synuclein".GLIA 55..11(2007):1178-1188
