ArticleNPJ Parkinson's disease2022
Cathepsin L-containing exosomes from α-synuclein-activated microglia induce neurotoxicity through the P2X7 receptor.
Article in NPJ Parkinson's disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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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.
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Who cites it
19 citing papers in PubMed, 32 citations in OpenAlex.
- Transplantation of Human IPSC-derived Microglia Ameliorates Neuropathology and Circuit Dysfunction in Progranulin-Deficient Mice.Research square · 2026Article
- Transplantation of Human IPSC-derived Microglia Ameliorates Neuropathology and Circuit Dysfunction in Progranulin-Deficient Mice.bioRxiv : the preprint server for biology · 2026Article
- Microglia heterogeneity and therapeutic strategies in Parkinson's disease.Frontiers in immunology · 2026Review
- Glioblastoma pathophysiology: roles of aging driven changes in STAT3 interactions with NF-κB dimer components in the modulation of the mitochondrial melatonergic pathway and night-time inflammation resolution.Exploration of targeted anti-tumor therapy · 2026Review
- Glial cell crosstalk in Parkinson's disease: Mechanisms, implications, and therapeutic strategies.Fundamental research · 2025Review
- Induced Pluripotent Stem Cells Derived Cellular Models for Investigating Parkinson's Disease Pathogenesis and Drug Screening.Stem cell reviews and reports · 2025Review
- Senescent Microglia Mediate Neuroinflammation-Induced Cognitive Dysfunction by Selective Elimination of Excitatory Synapses in the Hippocampal CA1.Aging cell · 2025Article
- New insights into pathogenisis and therapies of P2X7R in Parkinson's disease.NPJ Parkinson's disease · 2025Review
- Enhanced exosome secretion regulated by microglial P2X7R in the medullary dorsal horn contributes to pulpitis-induced pain.Cell & bioscience · 2025Article
- Elevated N-glycosylated cathepsin L impairs oocyte function and contributes to oocyte senescence during reproductive aging.Aging cell · 2025Article
- Trends in Research on the P2X7 Receptor: A Bibliometric and Visualization Analysis.Journal of inflammation research · 2025Review
- Stat3 mediates Fyn kinase-driven dopaminergic neurodegeneration and microglia activation.Disease models & mechanisms · 2024Article
- The Yin and Yang of Microglia-Derived Extracellular Vesicles in CNS Injury and Diseases.Cells · 2024Review
- Secretome - the role of extracellular vesicles in the pathogenesis and therapy of neurodegenerative diseases.Postepy psychiatrii neurologii · 2024Review
- Modulation of Microglial Function by ATP-Gated P2X7 Receptors: Studies in Rat, Mice and Human.Cells · 2024Review
- Dysregulation of kidney proteases in the pathogenesis of hypertension following unilateral nephrectomy in juvenile mice.American journal of translational research · 2024Article
- Role of the P2 × 7 receptor in neurodegenerative diseases and its pharmacological properties.Cell & bioscience · 2023Review
- Potential for Therapeutic-Loaded Exosomes to Ameliorate the Pathogenic Effects of α-Synuclein in Parkinson's Disease.Biomedicines · 2023Review
- Microglia activation in central nervous system disorders: A review of recent mechanistic investigations and development efforts.Frontiers in neurology · 2023Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Uncontrolled microglial activation is pivotal to the pathogenesis of Parkinson's disease (PD), which can secrete Cathepsin L (CTSL) to affect the survival of neurons in the PD patients; however, the precise mechanism has yet to be determined. We demonstrated for the first time that CTSL was mostly released by exosomes derived from α-Syn-activated microglia, resulting in neuronal damage and death. The elevation of CTSL activity was blocked by GW4869, suggesting a critical role for exosomes in mediating CTSL release. Furthermore, the P2X7R/PI3K/AKT signalling pathway was identified as the underlying molecular mechanism since specific antagonists of this signalling pathway, P2X7R knockdown and exosome release inhibitors significantly reduced the injury to cultured mouse cortical neurons. Our study suggests that increased extracellular release of CTSL from α-Syn-activated microglia through exosomes amplifies and aggravates of the neurotoxic effect of microglia, implying that CTSL may be involved in a fresh mechanism of PD pathogenesis, and serve as a potential biomarker and a target for PD drug development.
Identifiers
What Socratic 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 Socratic graph.