ArticlePloS one2016
Alpha-Synuclein Proteins Promote Pro-Inflammatory Cascades in Microglia: Stronger Effects of the A53T Mutant.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
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Who cites it
95 citing papers in PubMed, 155 citations in OpenAlex.
- The A53T Parkinson's Disease Mouse Model Shows Abnormal Outer Retinal OCT Metabolic Biomarker Patterns.Investigative ophthalmology & visual science · 2026Article
- KOLF2.1J iTF-Microglia: A standardized platform to study microglial transcriptional regulatory networks in CNS disease.iScience · 2026Article
- The anti-diabetic drug acarbose modulates the nucleation dependent amyloid fibrillation of wild-type α-synuclein.Journal of computer-aided molecular design · 2026Article
- Alpha-Synuclein Dynamics in Cerebral Ischemia.ASN neuro · 2026Review
- Molecular mechanisms underlying Parkinson's disease and role of phytochemicals, α-synuclein, sirtuins, and incretin mimetics in potential therapy.Frontiers in pharmacology · 2026Review
- Glycation of alpha-synuclein enhances aggregation and neuroinflammatory responses.NPJ Parkinson's disease · 2025Article
- The Interplay Between CBInternational journal of molecular sciences · 2025Article
- An update on the involvement of inflammatory mediators in Parkinson's disease pathogenesis.Archives of toxicology · 2025Review
- Templating of monomeric alpha-synuclein results in inflammation and SNpc dopamine neuron death in a genetic mouse model of induced synucleinopathy.Scientific reports · 2025Article
- Intermittent fasting reduces alpha-synuclein pathology and functional decline in a mouse model of Parkinson's disease.Nature communications · 2025Article
- Oligodendrocyte-specific overexpression of human alpha-synuclein results in elevated MBP levels and inflammatory responses in TgM83 mice, mimicking the pathological features of multiple system atrophy.Acta neuropathologica communications · 2025Article
- Park7 deletion leads to sex-specific transcriptome changes involving NRF2-CYP1B1 axis in mouse midbrain astrocytes.NPJ Parkinson's disease · 2025Article
- α-Synuclein pathology as a target in neurodegenerative diseases.Nature reviews. Neurology · 2025Review
- Unraveling Dysregulated Cell Signaling Pathways, Genetic and Epigenetic Mysteries of Parkinson's Disease.Molecular neurobiology · 2024Review
- The immune system in Parkinson's disease: what we know so far.Brain : a journal of neurology · 2024Review
- Blood-brain barrier alterations and their impact on Parkinson's disease pathogenesis and therapy.Translational neurodegeneration · 2024Review
- Interplay between α-synuclein and parkin genes: Insights of Parkinson's disease.Molecular biology reports · 2024Review
- What Can Inflammation Tell Us about Therapeutic Strategies for Parkinson's Disease?International journal of molecular sciences · 2024Review
- 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
- The Impact of Intestinal Microbiota and Toll-like Receptor 2 Signaling on α-Synuclein Pathology in Nontransgenic Mice Injected with α-Synuclein Preformed Fibrils.Microorganisms · 2024Article
35 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Parkinson's disease (PD) is histologically described by the deposition of α-synuclein, whose accumulation in Lewy bodies causes dopaminergic neuronal death. Although most of PD cases are sporadic, point mutations of the gene encoding the α-synuclein protein cause inherited forms of PD. There are currently six known point mutations that result in familial PD. Oxidative stress and neuroinflammation have also been described as early events associated with dopaminergic neuronal degeneration in PD. Though it is known that microglia are activated by wild-type α-synuclein, little is known about its mutated forms and the signaling cascades responsible for this microglial activation. The present study was designed to investigate consequences of wild-type and mutant α-synuclein (A53T, A30P and E46K) exposure on microglial reactivity. Interestingly, we described that α-synuclein-induced microglial reactivity appeared to be peptide-dependent. Indeed, the A53T protein activated more strongly microglia than the wild-type α-synuclein and other mutants. This A53T-induced microglial reactivity mechanism was found to depend on phosphorylation mechanisms mediated by MAPKs and on successive NFkB/AP-1/Nrf2 pathways activation. These results suggest that the microgliosis intensity during PD might depend on the type of α-synuclein protein implicated. Indeed, mutated forms are more potent microglial stimulators than wild-type α-synuclein. Based on these data, anti-inflammatory and antioxidant therapeutic strategies may be valid in order to reduce microgliosis but also to subsequently slow down PD progression, especially in familial cases.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.