Synuclein activates microglia in a model of Parkinson's disease.
Parkinson's disease (PD) is the most common neurodegenerative movement disorder afflicting >500,000 patients in the United States alone. This age-related progressive disorder is typified by invariant loss of dopaminergic substantia nigra neurons (DAN), dystrophic neurites, the presence of alpha-synuclein (SYN) positive intracytoplasmic inclusions (Lewy bodies) in the remaining DAN, and activated microglia. As such, microglial activation and resultant increase in proinflammatory molecules have moved to the forefront of PD research as a potential pathobiologic mechanism of disease. Herein, we present data demonstrating early microglial activation in mice that over-express wild-type SYN, the release of SYN from a SYN overexpressing MN9D cell line, and dose-dependent SYN-mediated activation of primary microglial cultures with consequent increases in proinflammatory molecules. Furthermore, we provide evidence that the CD36 scavenger receptor and downstream kinases are involved in SYN-mediated microglial activation. Together, our data suggest an early role for SYN and inflammation in PD pathogenesis.
Su
Xiaomin
X
Center for Aging and Developmental Biology, Aab Institute for Biomedical Research, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, NY 14642, USA.
Maguire-Zeiss
Kathleen A
KA
Giuliano
Rita
R
Prifti
Landa
L
Venkatesh
Karthik
K
Federoff
Howard J
HJ
D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism*; D020734:Parkinsonian Disorders / Q000378:metabolism*; D051843:Synucleins / Q000187:drug effects* / Q000378:metabolism*
D016207:Cytokines; D051843:Synucleins