Mutant α-Synuclein Overexpression Mediates Early Proinflammatory Activity
Open accessAbstract
Microglia provide immune surveillance for the brain through both the removal of cellular debris and protection against infection by microorganisms and "foreign" molecules. Upon activation, microglia display an altered morphology and increased expression of proinflammatory molecules. Increased numbers of activated microglia have been identified in a number of neurodegenerative diseases including Parkinson's disease (PD). What remains to be determined is whether activated microglia result from ongoing cell death or are involved in disease initiation and progression. To address this question we utilized a transgenic mouse model that expresses a mutated form of a key protein involved in Parkinson's disease, alpha-synuclein. Herein, we report an increase in activated microglia and proinflammatory molecules in 1-month-old transgenic mice well before cell death occurs in this model. Frank microglial activation is resolved by 6 months of age while a subset of proinflammatory molecules remain elevated for 12 months. Both tyrosine hydroxylase mRNA expression and alpha-synuclein protein are decreased in the striatum of older animals evidence of dystrophic neuritic projections. To determine whether mutated alpha-synuclein could directly activate microglia primary microglia-enriched cell cultures were treated with exogenous mutated alpha-synuclein. The data reveal an increase in activated microglia and proinflammatory molecules due to direct interaction with mutated alpha-synuclein. Together, these data demonstrate that mutated alpha-synuclein mediates a proinflammatory response in microglia and this activity may participate in PD pathogenesis.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
CD36 and P2X7 receptors are involved in microglial activation induced by α-syn.
“CD36 and P2X7 receptors are also involved in microglial activation induced by α-syn.”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [248]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 89 · Cited by 145
- Authors
- Su, X., Federoff, H. J., & Maguire-Zeiss, K. A.
- Affiliations
- University of Rochester Medicine (US)
- Georgetown University Medical Center (US)
- Venue
- Neurotoxicity Research
- Published
- 2009-04-28
- Volume
- 16
- Issue
- 3
- Pages
- 238-254
- ISSN
- 1029-8428 (ISSN-L)
- 1476-3524
- PMC
- PMC2877375
- OpenAlex
- W2064978332
- Cited by
- 145
- References
- 89
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 7 · 2023: 6 · 2022: 12 · 2021: 8 · 2020: 7 · 2019: 10 · 2018: 10 · 2017: 8 · 2016: 3 · 2015: 8 · 2014: 10 · 2013: 11 · 2012: 13
- FWCI
- 7.67
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neurotoxicity Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Environmental Health Sciences (R01ES014470)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- alpha-synuclein, Parkinson's disease, microglial activation, pro-inflammatory response, transgenic mouse model, striatum, tyrosine hydroxylase, dystrophic neurites, neuroinflammation, disease initiation
- MeSH terms
- Age Factors, Animals, Animals, Newborn, Calcium-Binding Proteins, Cells, Cultured, Cerebral Cortex, Disease Models, Animal, Gene Expression Regulation, Humans, Intermediate Filament Proteins, Mice, Inbred C57BL, Mice, Transgenic, Microfilament Proteins, Mutation, RNA, Messenger, Time Factors, Tyrosine 3-Monooxygenase, Cytokines, Reactive Oxygen Species, Microglia, CD36 Antigens, MPTP Poisoning, Mice, Nitric Oxide Synthase Type II
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
