Cited by 474Parkinson's Disease Mechanisms and TreatmentsNeuroinflammation and Neurodegeneration MechanismsNuclear Receptors and Signaling

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Synuclein activates microglia in a model of Parkinson's disease

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Su, Xiaomin, Maguire-Zeiss, Kathleen A., Giuliano, Rita, Prifti, Landa, Venkatesh, Karthik, Federoff, Howard J.·2008·Neurobiology of Aging

DOI 10.1016/j.neurobiolaging.2007.04.006PMC PMC2621109

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Abstract

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.

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Authors: Su, X., Maguire-Zeiss, K. A., Giuliano, R., Prifti, L., Venkatesh, K., & Federoff, H. J.
Affiliations: University of Rochester Medicine (US)
Corresponding author: Federoff, Howard J.
ORCID: Su, Xiaomin
Venkatesh, Karthik
Federoff, Howard J.
Venue: Neurobiology of Aging
Publisher: Elsevier BV
Published: 2008-11
Volume: 29
Issue: 11
Pages: 1690-1701
ISSN: 0197-4580 (ISSN-L)
DOI: 10.1016/j.neurobiolaging.2007.04.006
PMC: PMC2621109
OpenAlex: W2120997873
Cited by: 474
References: 86
Citations by year: 2026: 11 · 2025: 17 · 2024: 27 · 2023: 19 · 2022: 46 · 2021: 46 · 2020: 37 · 2019: 30 · 2018: 26 · 2017: 18 · 2016: 15 · 2015: 22 · 2014: 32 · 2013: 21 · 2012: 24
FWCI: 12.04
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neurobiology of Aging (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute of Neurological Disorders and Stroke (T32NS007489)
Topics: Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
Keywords: Parkinson's disease, alpha-synuclein, microglial activation, neuroinflammation, CD36 scavenger receptor, proinflammatory molecules, Lewy bodies, MN9D cells, pathogenesis
MeSH terms: Animals, Cell Line, Disease Models, Animal, Humans, Male, Mice, Inbred C57BL, Mice, Transgenic, Cytokines, Microglia, Parkinsonian Disorders, Mice, Synucleins

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Synuclein activates microglia in a model of Parkinson's disease

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