ArticleActa neuropathologica communications2018
Membrane binding, internalization, and sorting of alpha-synuclein in the cell.
Article in Acta neuropathologica communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.
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Who cites it
56 citing papers in PubMed, 1 synthesis or guideline pooled it, 96 citations in OpenAlex.
- Inter-organellar Communication in Parkinson's and Alzheimer's Disease: Looking Beyond Endoplasmic Reticulum-Mitochondria Contact Sites.Frontiers in neuroscience · 2022Pooled it
- Sleep-circadian modulation of autophagy and glymphatic function: failure of coordinated brain clearance in Parkinson's disease.NPJ Parkinson's disease · 2026Review
- Determination of α-Synuclein Protein Interactions by μMap Photoproximity Labeling.Journal of the American Chemical Society · 2026Article
- Alpha-Synuclein in Neurodegeneration: From Shared Biology to Disease-Specific Phenotypes.Cells · 2026Review
- In vivo Proximity & Spatial Proteomics with CRISPR Screening Identify STXBP1 as a Protective Modifier of α-synuclein Toxicity in Dopamine Neurons.bioRxiv : the preprint server for biology · 2026Article
- Internalized SNCA/α-synuclein fibrils become truncated and resist degradation in neurons while glial cells rapidly degrade SNCA fibrils.Autophagy · 2026Article
- Propagation of α-synuclein pathology: models, mechanisms and future goals.Molecular neurodegeneration advances · 2026Review
- Determination of α-Synuclein Protein Interactions by μMap Photo-proximity Labeling.bioRxiv : the preprint server for biology · 2025Article
- Alpha-Synuclein as a Potential Biomarker for Inclusion Body Myositis in Blood and Muscle.Neuropathology and applied neurobiology · 2025Article
- Article
- USP19 deubiquitinase inactivation regulates α-synuclein ubiquitination and inhibits accumulation of Lewy body-like aggregates in mice.NPJ Parkinson's disease · 2023Article
- Genome-wide CRISPR-Cas9 Knockout Screening Reveals a TSPAN3-mediated Endo-lysosome Pathway Regulating the Degradation of α-Synuclein Oligomers.Molecular neurobiology · 2023Article
- Characterization of the pathogenic α-Synuclein Variant V15A in Parkinson´s disease.NPJ Parkinson's disease · 2023Article
- More than meets the eye in Parkinson's disease and other synucleinopathies: from proteinopathy to lipidopathy.Acta neuropathologica · 2023Review
- α-Synuclein and biological membranes: the danger of loving too much.Chemical communications (Cambridge, England) · 2023Review
- Overexpression of alpha synuclein disrupts APP and Endolysosomal axonal trafficking in a mouse model of synucleinopathy.Neurobiology of disease · 2023Article
- α-Synuclein is required for sperm exocytosis at a post-fusion stage.Frontiers in cell and developmental biology · 2023Article
- Exercise-Induced Autophagy Ameliorates Motor Symptoms Progressivity in Parkinson's Disease Through Alpha-Synuclein Degradation: A Review.Neuropsychiatric disease and treatment · 2023Review
- Membrane-Binding Biomolecules Influence the Rate of Vesicle Exchange between Bacteria.Applied and environmental microbiology · 2022Article
- Amelioration of pathologic α-synuclein-induced Parkinson's disease by irisin.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alpha-synuclein (aSyn) plays a crucial role in Parkinson's disease (PD) and other synucleinopathies, since it misfolds and accumulates in typical proteinaceous inclusions. While the function of aSyn is thought to be related to vesicle binding and trafficking, the precise molecular mechanisms linking aSyn with synucleinopathies are still obscure. aSyn can spread in a prion-like manner between interconnected neurons, contributing to the propagation of the pathology and to the progressive nature of synucleinopathies. Here, we investigated the interaction of aSyn with membranes and trafficking machinery pathways using cellular models of PD that are amenable to detailed molecular analyses. We found that different species of aSyn can enter cells and form high molecular weight species, and that membrane binding properties are important for the internalization of aSyn. Once internalized, aSyn accumulates in intracellular inclusions. Interestingly, we found that internalization is blocked in the presence of dynamin inhibitors (blocked membrane scission), suggesting the involvement of the endocytic pathway in the internalization of aSyn. By screening a pool of small Rab-GTPase proteins (Rabs) which regulate membrane trafficking, we found that internalized aSyn partially colocalized with Rab5A and Rab7. Initially, aSyn accumulated in Rab4A-labelled vesicles and, at later stages, it reached the autophagy-lysosomal pathway (ALP) where it gets degraded. In total, our study emphasizes the importance of membrane binding, not only as part of the normal function but also as an important step in the internalization and subsequent accumulation of aSyn. Importantly, we identified a fundamental role for Rab proteins in the modulation of aSyn processing, clearance and spreading, suggesting that targeting Rab proteins may hold important therapeutic value in PD and other synucleinopathies.
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