Cited by 1,265Parkinson's Disease Mechanisms and TreatmentsNeuroinflammation and Neurodegeneration MechanismsNuclear Receptors and Signaling

The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index.

Aggregated α‐synuclein activates microglia: a process leading to disease progression in Parkinson's disease

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.

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Crossref · 10.1096/fj.04-2751com

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  1. Block M. L. Wu X. Pei Z. Li G. Wang T. Qin L. Wilson B. Yang J. Hong J. S. andVeronesi B.(2004)The selective dopaminergic neurotoxicity of nanometer size diesel exhaust particles is mediated by microglia.FASEB J.In press

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Metadata

Authors
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.
Affiliations
  • National Institutes of Health (US)
  • Dalian Medical University (CN)
  • University of Washington (US)
Venue
The FASEB Journal
Publisher
Wiley
Published
2005-04
Volume
19
Issue
6
Pages
533-542
ISSN
  • 0892-6638 (ISSN-L)
  • 1530-6860
OpenAlex
W2128631317
Cited by
1,265
References
50
Citations by year
2026: 30 · 2025: 57 · 2024: 95 · 2023: 51 · 2022: 97 · 2021: 80 · 2020: 69 · 2019: 76 · 2018: 85 · 2017: 51 · 2016: 59 · 2015: 71 · 2014: 67 · 2013: 60 · 2012: 69
FWCI
23.37
Type
journal article
Language
en
Open access
closed
Locations
  • The FASEB Journal (publishedVersion)
  • PubMed (publishedVersion)
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
alpha-synuclein aggregation, microglial activation, Parkinson's disease, substantia nigra, dopaminergic neuron loss, NADPH oxidase, reactive oxygen species, phagocytosis, neuroinflammation, Lewy bodies, neurotoxicity, disease progression
MeSH terms
Animals, Astrocytes, Brain, Cells, Cultured, Dopamine, Embryo, Mammalian, Enzyme Activation, gamma-Aminobutyric Acid, Humans, Immunohistochemistry, Mesencephalon, Nerve Degeneration, Neuroglia, Neurons, Nitric Oxide, Nitrites, Parkinson Disease, Phagocytosis, Polymers, Rats, Inbred F344, Recombinant Proteins, Substantia Nigra, Tritium, Tumor Necrosis Factor-alpha, Tyrosine 3-Monooxygenase, Dinoprostone, Reactive Oxygen Species, Microglia, Mice, Knockout, Oxidative Stress, NADPH Oxidases, Mice, Rats, alpha-Synuclein

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