ArticleThe Journal of biological chemistry2010
Direct transfer of alpha-synuclein from neuron to astroglia causes inflammatory responses in synucleinopathies.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 522 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
522 citing papers in PubMed, 1 synthesis or guideline pooled it, 876 citations in OpenAlex.
- Neuroprotective Effects of Resveratrol in In vivo and In vitro Experimental Models of Parkinson's Disease: a Systematic Review.Neurotoxicity research · 2022Pooled it
- Astrocytic cathepsin D promotes α-synuclein processing and Lewy neurite-like aggregate maturation.EMBO reports · 2026Article
- Convergent Astrocytic Failure in Parkinson's Disease: A System-Level Model of Pathogenesis and Treatment.Molecular neurobiology · 2026Review
- When Pathologies Collide: The Intersection of Tau and Alpha-Synuclein in Neurodegenerative Diseases.Molecular neurobiology · 2026Review
- Cholesterol dysregulation in APOE4 astrocytes promotes α-synuclein pathology in miBrains.Cell stem cell · 2026Article
- Fluoride exposure induces oxidative damage in primary astrocytes of SD rats and changes in the expression of α-synuclein and its effect on Nrf2-NQO1/HO-1 signaling pathway.Journal of bioenergetics and biomembranes · 2026Article
- Neurodegenerative diseases and immune system: From pathogenic mechanism to therapy.Neural regeneration research · 2026Article
- Altered light-dark phase-dependent behavioral responses and suprachiasmatic nucleus pathology in an α-synuclein rat model of Parkinson's disease.NPJ Parkinson's disease · 2026Article
- Role of dysregulated calcium homeostasis in astrocytes in neurodegenerative disorders.Nature reviews. Neuroscience · 2026Review
- Strategies for Optimizing Genetic Mouse Models to Enhance the Understanding of Parkinson's Disease.Biomedicines · 2026Review
- Toxic Alpha-Synuclein and the Opening of the Gate: Blood-Brain Barrier Damage and Stepwise Leukocyte Infiltration.Cellular and molecular neurobiology · 2026Review
- The Brain-Gut Axis in Parkinson's Disease Pathology.Comprehensive Physiology · 2026Review
- Anti-TLR2 immunotherapy modulates neuron-to-oligodendrocyte propagation of α-synuclein in mouse and human models.Nature communications · 2026Article
- Neuroimmune Interactions in Neurodegeneration: The Role of Microglia in Alzheimer's and Parkinson's Disease Pathogenesis.Brain sciences · 2026Review
- Impairment in stimulus-response learning as a cognitive biomarker in a model of synucleinopathy.Translational psychiatry · 2026Article
- Propagation of α-synuclein pathology: models, mechanisms and future goals.Molecular neurodegeneration advances · 2026Review
- Molecular mechanisms underlying Parkinson's disease and role of phytochemicals, α-synuclein, sirtuins, and incretin mimetics in potential therapy.Frontiers in pharmacology · 2026Review
- Neurovascular dysfunction in the development and progression of neuroinflammatory diseases.Frontiers in cellular neuroscience · 2026Review
- Robust immunohistochemical detection of α-synuclein, tau and amyloid-β in human brain tissue archived for up to 78 years.Free neuropathology · 2026Article
- Decoding the brain's ATG8 paralog code: LC3-GABARAP specialization at synapses and the astrocyte-neuron interface.Frontiers in cell and developmental biology · 2026Review
462 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Abnormal neuronal aggregation of alpha-synuclein is implicated in the development of many neurological disorders, including Parkinson disease and dementia with Lewy bodies. Glial cells also show extensive alpha-synuclein pathology and may contribute to disease progression. However, the mechanism that produces the glial alpha-synuclein pathology and the interaction between neurons and glia in the disease-inflicted microenvironment remain unknown. Here, we show that alpha-synuclein proteins released from neuronal cells are taken up by astrocytes through endocytosis and form inclusion bodies. The glial accumulation of alpha-synuclein through the transmission of the neuronal protein was also demonstrated in a transgenic mouse model expressing human alpha-synuclein. Furthermore, astrocytes that were exposed to neuronal alpha-synuclein underwent changes in the gene expression profile reflecting an inflammatory response. Induction of pro-inflammatory cytokines and chemokines correlated with the extent of glial accumulation of alpha-synuclein. Together, these results suggest that astroglial alpha-synuclein pathology is produced by direct transmission of neuronal alpha-synuclein aggregates, causing inflammatory responses. This transmission step is thus an important mediator of pathogenic glial responses and could qualify as a new therapeutic target.
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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.