ArticleJournal of neuroinflammation2022
A breakdown in microglial metabolic reprogramming causes internalization dysfunction of α-synuclein in a mouse model of Parkinson's disease.
Article in Journal of neuroinflammation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 75 citations in OpenAlex.
- Microglia-targetedMaterials today. Bio · 2026Article
- Molecular target for neuroinflammation and pain management: transient receptor potential vanilloid 1.Inflammopharmacology · 2026Review
- Regional reduction of high-energy phosphorus metabolites characterizes the cerebellar subtype of multiple system atrophy.NPJ Parkinson's disease · 2026Article
- Review
- Inhibition of Microglial TRPV1 Ameliorates Brain Injury After Intracerebral Hemorrhage by Suppressing AMPK/PINK1-Mediated Mitophagy.CNS neuroscience & therapeutics · 2026Article
- Sex Differences in Metabolite-Immune Circuits of Neuroinflammation.Immunological reviews · 2026Review
- Microglia-Neuron Crosstalk: An Intimate Molecular Conversation in Neurodegeneration.International journal of molecular sciences · 2026Review
- From metabolism to neurodegeneration: how microglial functional reprogramming drives neurodegenerative diseases.Frontiers in molecular neuroscience · 2026Review
- Cuproptosis-associated genesFrontiers in immunology · 2026Article
- Neuroinflammation and metabolic reprogramming in Parkinson's disease.Frontiers in immunology · 2026Review
- Hv1 inhibition rescues AD pathology by restoring microglial mitochondrial function and enhancing mitochondrial transfer.Experimental & molecular medicine · 2025Article
- Capsaicin Alleviates Autophagy-Lysosomal Dysfunction via PPARA-Mediated V-ATPase Subunit ATP6V0E1 Signaling in 3xTg-AD Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Metabolic Profiling Reveals a Glycolytic Shift and an IRG1/Itaconate/NF2L2 Axis Regulating Neurotoxic Oxidative Stress in Inflammatory Microglia.Journal of neurochemistry · 2025Article
- Interplay of α-Synuclein Oligomers and Endoplasmic Reticulum Stress in Parkinson'S Disease: Insights into Cellular Dysfunctions.Inflammation · 2025Review
- Targeting CX3CR1 Signaling Dynamics: A Critical Determinant in the Temporal Regulation of Post-Stroke Neurorepair.Brain sciences · 2025Review
- Liver-specific expression of ANGPTL8 promotes Alzheimer's disease progression through activating microglial pyroptosis.Journal of neuroinflammation · 2025Article
- THSG counteracts microglial glycolytic reprogramming and neuronal necroptosis both in vivo and in vitro under conditions of neuroinflammation.Scientific reports · 2025Article
- Glucose Metabolic Reprogramming in Microglia: Implications for Neurodegenerative Diseases and Targeted Therapy.Molecular neurobiology · 2025Review
- Metabolic Dysregulation in Parkinson's Disease: Non-Oxidative Phosphorylation and Its Role in Brain Energy Metabolism.Aging and disease · 2025Review
- Immune cell metabolic dysfunction in Parkinson's disease.Molecular neurodegeneration · 2025Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe α-synuclein released by neurons activates microglia, which then engulfs α-synuclein for degradation via autophagy. Reactive microglia are a major pathological feature of Parkinson's disease (PD), although the exact role of microglia in the pathogenesis of PD remains unclear. Transient receptor potential vanilloid type 1 (TRPV1) channels are nonselective cation channel protein that have been proposed as neuroprotective targets in neurodegenerative diseases.
methodsUsing metabolic profiling, microglia energy metabolism was measured including oxidative phosphorylation and aerobic glycolysis. The mRFP-GFP-tagged LC3 reporter was introduced to characterize the role of TRPV1 in microglial autophagy. α-synuclein preformed fibril (PFF) TRPV1
resultsWe found that acute exposure to PFF caused microglial activation as a result of metabolic reprogramming from oxidative phosphorylation to aerobic glycolysis via the AKT-mTOR-HIF-1α pathway. Activated microglia eventually reached a state of chronic PFF-tolerance, accompanied by broad defects in energy metabolism. We showed that metabolic boosting by treatment with the TRPV1 agonist capsaicin rescued metabolic impairments in PFF-tolerant microglia and also defects in mitophagy caused by disruption of the AKT-mTOR-HIF-1α pathway. Capsaicin attenuated phosphorylation of α-synuclein in primary neurons by boosting phagocytosis in PFF-tolerant microglia in vitro. Finally, we found that behavioral deficits and loss of dopaminergic neurons were accelerated in the PFF TRPV1
conclusionThe findings suggest that modulating microglial metabolism might be a new therapeutic strategy for PD.
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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.