ArticleJournal of neuroinflammation2021
Metabotropic glutamate receptor 5 inhibits α-synuclein-induced microglia inflammation to protect from neurotoxicity in Parkinson's disease.
Article in Journal of neuroinflammation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- Pre-clinical Studies Identifying Molecular Pathways of Neuroinflammation in Parkinson's Disease: A Systematic Review.Frontiers in aging neuroscience · 2022Pooled it
- Targeting GPCR Signaling in Parkinson's Disease: From Molecular Pathology to Exercise-Based Therapeutics.Molecular neurobiology · 2026Review
- Proteasome Dysfunction and Aggregation-Prone Proteins in Neurodegenerative Diseases: From Mechanisms to Therapeutic Opportunities.International journal of molecular sciences · 2026Review
- Uncovering the role of c-Fos in the bidirectional relationship between depression/anxiety behaviors and α-synuclein propagation in Parkinson's disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Sex-dependent immune activation shapes disease progression in a model of Parkinson's disease.Biology of sex differences · 2025Article
- Decoding the multifaceted cellular and transcriptomic variations of natural killer cells generated from patients with Parkinson's disease.Scientific reports · 2025Article
- Induced Pluripotent Stem Cells Derived Cellular Models for Investigating Parkinson's Disease Pathogenesis and Drug Screening.Stem cell reviews and reports · 2025Review
- NOSH-aspirin (NBS-1120) attenuates motor defects and dopaminergic neuron degeneration in a rat model of Parkinson's disease.European journal of pharmacology · 2025Article
- mGluR5 as a Potential Orchestrator of Astrocyte Interactions in Neurological Disorders.Neural plasticity · 2025Review
- Insights into the Metabolism, Disposition, and Quantitative Profile of mGlu5 NAM AE90015 with Metabolite Identification and a Novel Integration Method.Molecules (Basel, Switzerland) · 2024Article
- NMDA receptor blockade attenuates Japanese encephalitis virus infection-induced microglia activation.Journal of neuroinflammation · 2024Article
- Enhanced mGluRCell death & disease · 2024Article
- GET73 modulates lipopolysaccharide- and ethanol-induced increase in cytokine/chemokine levels in primary cultures of microglia of rat cerebral cortex.Pharmacological reports : PR · 2024Article
- Sodium butyrate activates the KImmunity, inflammation and disease · 2024Article
- 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
- Relationship among α‑synuclein, aging and inflammation in Parkinson's disease (Review).Experimental and therapeutic medicine · 2024Review
- Hua-Feng-Dan Alleviates LPS-induced Neuroinflammation by Inhibiting the TLR4/Myd88/NF-κB Pathway: Integrating Network Pharmacology and Experimental Validation.Current pharmaceutical design · 2024Article
- The Role of Ocimene in Decreasing α-Synuclein Aggregation using Rotenone-induced Rat Model.Central nervous system agents in medicinal chemistry · 2024Article
- Amyloid-βiScience · 2023Article
- Glutamate Receptor Dysregulation and Platelet Glutamate Dynamics in Alzheimer's and Parkinson's Diseases: Insights into Current Medications.Biomolecules · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundMicroglia activation induced by α-synuclein (α-syn) is one of the most important factors in Parkinson's disease (PD) pathogenesis. However, the molecular mechanisms by which α-syn exerts neuroinflammation and neurotoxicity remain largely elusive. Targeting metabotropic glutamate receptor 5 (mGluR5) has been an attractive strategy to mediate microglia activation for neuroprotection, which might be an essential regulator to modulate α-syn-induced neuroinflammation for the treatment of PD. Here, we showed that mGluR5 inhibited α-syn-induced microglia inflammation to protect from neurotoxicity in vitro and in vivo.
methodsCo-immunoprecipitation assays were utilized to detect the interaction between mGluR5 and α-syn in microglia. Griess, ELISA, real-time PCR, western blotting, and immunofluorescence assays were used to detect the regulation of α-syn-induced inflammatory signaling, cytokine secretion, and lysosome-dependent degradation.
resultsα-syn selectively interacted with mGluR5 but not mGluR3, and α-syn N terminal deletion region was essential for binding to mGluR5 in co-transfected HEK293T cells. The interaction between these two proteins was further detected in BV2 microglia, which was inhibited by the mGluR5 specific agonist CHPG without effect by its selective antagonist MTEP. Moreover, in both BV2 cells and primary microglia, activation of mGluR5 by CHPG partially inhibited α-syn-induced inflammatory signaling and cytokine secretion and also inhibited the microglia activation to protect from neurotoxicity. We further found that α-syn overexpression decreased mGluR5 expression via a lysosomal pathway, as evidenced by the lysosomal inhibitor, NH
conclusionsThese findings provided evidence for a novel mechanism by which the association of α-syn with mGluR5 was attributed to α-syn-induced microglia activation via modulation of mGluR5 degradation and its intracellular signaling. This may be a new molecular target for an effective therapeutic strategy for PD pathology.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.