ArticleProceedings of the National Academy of Sciences of the United States of America2022
Therapeutic functions of astrocytes to treat α-synuclein pathology in Parkinson's disease.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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46 citing papers in PubMed, 56 citations in OpenAlex.
- Disarming CH25H to clear α-synuclein.Trends in molecular medicine · 2026Article
- Astrocytes orchestrate neuroprotection and pathogenesis via bidirectional neuronal interactions in Parkinson's disease.Journal of physiology and biochemistry · 2026Review
- Neurodegenerative diseases and immune system: From pathogenic mechanism to therapy.Neural regeneration research · 2026Article
- Protein disulfide isomerase dissolves and detoxifies oligomeric assemblies of amyloid beta peptide.FEBS letters · 2026Article
- Reactive astrocytes mediate toxicity in iPSC derived dopaminergic neurons.NPJ Parkinson's disease · 2026Article
- Astrocytic ACSBG1 depletion improves lipid-cytokine signaling and attenuates α-Synuclein pathology in a Parkinson's disease mouse model.bioRxiv : the preprint server for biology · 2026Article
- Sleep-circadian modulation of autophagy and glymphatic function: failure of coordinated brain clearance in Parkinson's disease.NPJ Parkinson's disease · 2026Review
- Dysregulation of astrocytic DNAJC6 contributes to sporadic Parkinson's disease pathogenesis.The Journal of clinical investigation · 2026Article
- Review
- Review
- A microbiome quantitative trait locus in SLC39A8 modulates disease severity in synucleinopathy-induced models of Parkinson's disease.Human molecular genetics · 2026Article
- Microglia, Astrocytes, and Oligodendrocytes in Parkinson's Disease: Neuroinflammatory Crosstalk and Emerging Therapeutic Strategies.Biomolecules · 2026Review
- Unlocking Parkinson's disease: harnessing the untapped potential of fatty acid metabolism in disease pathogenesis.Frontiers in immunology · 2026Review
- From Neuron-Centric to Glia-Centric: How Aging Glial Networks Drive Neurodegenerative Disease.Journal of neurochemistry · 2026Review
- Dysregulated proteostasis in p.A53T-α-Synuclein astrocytes aggravates Lewy-like neuropathology in a Parkinson's disease iPSC model.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Changes in neural progenitor lineage composition during astrocytic differentiation of human iPSCs.eLife · 2025Article
- Extracellular LCN2 Binding to 24p3R in Astrocytes Impedes α-Synuclein Endocytosis in Parkinson's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Diversity, Functional Complexity, and Translational Potential of Glial Cells in the Central Nervous System.International journal of molecular sciences · 2025Review
- Recent Advances in Autophagy and Immunotherapy for the Clearance of Aggregated α-Synuclein in Parkinson's Disease.Aging and disease · 2025Review
- Glial phagocytosis for synapse and toxic proteins in neurodegenerative diseases.Molecular neurodegeneration · 2025Review
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intraneuronal inclusions of misfolded α-synuclein (α-syn) and prion-like spread of the pathologic α-syn contribute to progressive neuronal death in Parkinson's disease (PD). Despite the pathologic significance, no efficient therapeutic intervention targeting α-synucleinopathy has been developed. In this study, we provide evidence that astrocytes, especially those cultured from the ventral midbrain (VM), show therapeutic potential to alleviate α-syn pathology in multiple in vitro and in vivo α-synucleinopathic models. Regulation of neuronal α-syn proteostasis underlies the therapeutic function of astrocytes. Specifically, VM-derived astrocytes inhibited neuronal α-syn aggregation and transmission in a paracrine manner by correcting not only intraneuronal oxidative and mitochondrial stresses but also extracellular inflammatory environments, in which α-syn proteins are prone to pathologic misfolding. The astrocyte-derived paracrine factors also promoted disassembly of extracellular α-syn aggregates. In addition to the aggregated form of α-syn, VM astrocytes reduced total α-syn protein loads both by actively scavenging extracellular α-syn fibrils and by a paracrine stimulation of neuronal autophagic clearance of α-syn. Transplantation of VM astrocytes into the midbrain of PD model mice alleviated α-syn pathology and protected the midbrain dopamine neurons from neurodegeneration. We further showed that cografting of VM astrocytes could be exploited in stem cell-based therapy for PD, in which host-to-graft transmission of α-syn pathology remains a critical concern for long-term cell therapeutic effects.
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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.