ArticleFrontiers in neuroscience2020
MMP13 Expression Is Increased Following Mutant α-Synuclein Exposure and Promotes Inflammatory Responses in Microglia.
Article in Frontiers in neuroscience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 15 citations in OpenAlex.
- The Potential Use of Matrix Metalloproteinases in Alzheimer's Disease Therapy.Journal of clinical medicine · 2026Review
- Sustained Transcriptional Response to Lipopolysaccharide and Interleukin-4 in an Immortalized Mouse Microglial Cell Line.Molecular neurobiology · 2026Article
- Regulation of matrix metalloproteinase-13 in cancer: Signaling pathways and non-coding RNAs in tumor progression and therapeutic targeting.World journal of clinical oncology · 2025Review
- The involvement of α-synucleinopathy in the disruption of microglial homeostasis contributes to the pathogenesis of Parkinson's disease.Cell communication and signaling : CCS · 2024Review
- Disulfidptosis-associated lncRNAs predict breast cancer subtypes.Scientific reports · 2023Article
- Exploring the mechanism of luteolin by regulating microglia polarization based on network pharmacology and in vitro experiments.Scientific reports · 2023Article
- The Interplay between α-Synuclein and Microglia in α-Synucleinopathies.International journal of molecular sciences · 2023Review
- Shared Inflammatory Pathology of Stroke and COVID-19.International journal of molecular sciences · 2022Review
- Comparative Study of Protein Aggregation Propensity and Mutation Tolerance Between Naked Mole-Rat and Mouse.Genome biology and evolution · 2022Article
- The immunomodulatory role of matrix metalloproteinases in colitis-associated cancer.Frontiers in immunology · 2022Review
- Apoptosis-associated speck-like protein containing a CARD-mediated release of matrix metalloproteinase 10 stimulates a change in microglia phenotype.Frontiers in molecular neuroscience · 2022Article
- The Contribution of Microglia to Neuroinflammation in Parkinson's Disease.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
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Abstract
α-Synuclein is a 140-amino acid protein that readily misfolds and is associated with the Lewy body pathology found in sporadic and genetic forms of Parkinson's disease. We and others have shown that wild-type α-synuclein is a damage-associated molecular pattern that directly elicits a proinflammatory response in microglia through toll-like receptor activation. Here we investigated the direct effect of oligomeric mutant α-synuclein (A53T) on microglia morphology and activation. We found that misfolded A53T increased quantitative measures of amoeboid cell morphology, NFκB nuclear translocation and the expression of prototypical proinflammatory molecules. We also demonstrated that A53T increased expression of MMP13, a matrix metalloproteinase that remodels the extracellular matrix. To better understand the role of MMP13 in synucleinopathies, we further characterized the role of MMP13 in microglial signaling. We showed exposure of microglia to MMP13 induced a change in morphology and promoted the release of TNFα and MMP9. Notably, IL1β was not released indicating that the pathway involved in MMP13 activation of microglia may be different than the A53T pathway. Lastly, MMP13 increased the expression of CD68 suggesting that the lysosomal pathway might be altered by this MMP. Taken together this study shows that mutant α-synuclein directly induces a proinflammatory phenotype in microglia, which includes the expression of MMP13. In turn, MMP13 directly alters microglia supporting the need for multi-target therapies to treat Parkinson's disease patients.
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