ArticleFluids and barriers of the CNS2022
Polarized α-synuclein trafficking and transcytosis across brain endothelial cells via Rab7-decorated carriers.
Article in Fluids and barriers of the CNS, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 37 citations in OpenAlex.
- Exosome Biology at the Interface of Neurodegeneration and Therapeutic Innovation.Molecular neurobiology · 2026Review
- Sleep-circadian modulation of autophagy and glymphatic function: failure of coordinated brain clearance in Parkinson's disease.NPJ Parkinson's disease · 2026Review
- Elevated plasma levels of alpha-synuclein are dispensable for Parkinson's disease pathology.NPJ Parkinson's disease · 2025Article
- Article
- From blood vessels to brain cells: Connecting the circulatory system and Parkinson's disease.Journal of Parkinson's disease · 2025Review
- The role of transcytosis in the blood-retina barrier: from pathophysiological functions to drug delivery.Frontiers in pharmacology · 2025Review
- Blood-brain barrier alterations and their impact on Parkinson's disease pathogenesis and therapy.Translational neurodegeneration · 2024Review
- Regulation of fatty acid delivery to metastases by tumor endothelium.bioRxiv : the preprint server for biology · 2024Article
- Review
- Aquaporin-4 and Parkinson's Disease.International journal of molecular sciences · 2024Review
- An AAV capsid reprogrammed to bind human Transferrin Receptor mediates brain-wide gene delivery.bioRxiv : the preprint server for biology · 2023Article
- Subcellular trafficking and transcytosis efficacy of different receptor types for therapeutic antibody delivery at the blood‒brain barrier.Fluids and barriers of the CNS · 2023Article
- Myo1d promotes alpha-synuclein transfer from brain microvascular endothelial cells to pericytes through tunneling nanotubes.iScience · 2023Article
- The cervical lymph node contributes to peripheral inflammation related to Parkinson's disease.Journal of neuroinflammation · 2023Article
- Blood-brain barrier endothelial cells in neurodegenerative diseases: Signals from the "barrier".Frontiers in neuroscience · 2023Review
- Mucopolysaccharidoses and the blood-brain barrier.Fluids and barriers of the CNS · 2022Review
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Parkinson's disease is mainly caused by aggregation of α-synuclein (α-syn) in the brain. Exchange of α-syn between the brain and peripheral tissues could have important pathophysiological and therapeutic implications, but the trafficking mechanism of α-syn across the blood brain-barrier (BBB) remains unclear. In this study, we therefore investigated uptake and transport mechanisms of α-syn monomers and oligomers across an in vitro BBB model system. Both α-syn monomers and oligomers were internalized by primary brain endothelial cells, with increased restriction of oligomeric over monomeric transport. To enlighten the trafficking route of monomeric α-syn in brain endothelial cells, we investigated co-localization of α-syn and intracellular markers of vesicular transport. Here, we observed the highest colocalization with clathrin, Rab7 and VPS35, suggesting a clathrin-dependent internalization, preferentially followed by a late endosome retromer-connected trafficking pathway. Furthermore, STED microscopy revealed monomeric α-syn trafficking via Rab7-decorated carriers. Knockdown of Caveolin1, VPS35, and Rab7 using siRNA did not affect monomeric α-syn uptake into endothelial cells. However, it significantly reduced transcytosis of monomeric α-syn in the luminal-abluminal direction, suggesting a polarized regulation of monomeric α-syn vesicular transport. Our findings suggest a direct role for Rab7 in polarized trafficking of monomeric α-syn across BBB endothelium, and the potential of Rab7 directed trafficking to constitute a target pathway for new therapeutic strategies against Parkinson's disease and related synucleinopathies.
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