ArticleScientific reports2022
Pericytes take up and degrade α-synuclein but succumb to apoptosis under cellular stress.
Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- Friend or foe? Glial-vascular interactions in health and neurodegenerative disease.Pharmacological reviews · 2026Review
- Human brain pericytes protect the blood-brain barrier from triple-negative breast cancer cells while promoting tumor aggressiveness.Journal of cell communication and signaling · 2026Article
- Association Between Blood-Brain Barrier Disruption and Gut Microbiota Dysbiosis in Parkinson's Disease.Cellular and molecular neurobiology · 2026Review
- Toxic Alpha-Synuclein and the Opening of the Gate: Blood-Brain Barrier Damage and Stepwise Leukocyte Infiltration.Cellular and molecular neurobiology · 2026Review
- Central nervous system pericytes express soluble ST2 in inflammation and injury.Molecular brain · 2026Article
- Interconnected roles of astrocytes and the blood-brain barrier in Parkinson's disease: pathological evidence, mechanistic insights, and knowledge gaps.Frontiers in aging neuroscience · 2026Review
- MAFF as a potential novel protective factor against Parkinson's disease: evidence from Mendelian randomization and single-cell RNA sequencing.Frontiers in aging neuroscience · 2026Article
- Pericytes in the optic nerve head.Progress in retinal and eye research · 2025Review
- In vitro models of microglia: a comparative study.Scientific reports · 2025Article
- α-Synuclein Degradation in Brain Pericytes Is Mediated via Akt, ERK, and p38 MAPK Signaling Pathways.International journal of molecular sciences · 2025Article
- New insights into the role of ubiquitination in angiogenesis (Review).International journal of molecular medicine · 2025Review
- Mutated LRRK2 induces a reactive phenotype and alters migration in human iPSC-derived pericyte-like cells.Fluids and barriers of the CNS · 2024Article
- Blood-brain barrier alterations and their impact on Parkinson's disease pathogenesis and therapy.Translational neurodegeneration · 2024Review
- The contribution of β-amyloid, Tau and α-synuclein to blood-brain barrier damage in neurodegenerative disorders.Acta neuropathologica · 2024Review
- Aggregate-prone brain regions in Parkinson's disease are rich in unique N-terminus α-synuclein conformers with high proteolysis susceptibility.NPJ Parkinson's disease · 2024Article
- Wrapping up the role of pericytes in Parkinson's disease.Neural regeneration research · 2023Article
- Myo1d promotes alpha-synuclein transfer from brain microvascular endothelial cells to pericytes through tunneling nanotubes.iScience · 2023Article
- Cultured brain pericytes adopt an immature phenotype and require endothelial cells for expression of canonical markers and ECM genes.Frontiers in cellular neuroscience · 2023Article
- Multiple system atrophy: α-Synuclein strains at the neuron-oligodendrocyte crossroad.Molecular neurodegeneration · 2022Review
- Human pericytes degrade diverse α-synuclein aggregates.PloS one · 2022Article
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Parkinson's disease (PD) is characterised by the progressive loss of midbrain dopaminergic neurons and the presence of aggregated α-synuclein (α-syn). Pericytes and microglia, two non-neuronal cells contain α-syn in the human brain, however, their role in disease processes is poorly understood. Pericytes, found surrounding the capillaries in the brain are important for maintaining the blood-brain barrier, controlling blood flow and mediating inflammation. In this study, primary human brain pericytes and microglia were exposed to two different α-synuclein aggregates. Inflammatory responses were assessed using immunocytochemistry, cytometric bead arrays and proteome profiler cytokine array kits. Fixed flow cytometry was used to investigate the uptake and subsequent degradation of α-syn in pericytes. We found that the two α-syn aggregates are devoid of inflammatory and cytotoxic actions on human brain derived pericytes and microglia. Although α-syn did not induce an inflammatory response, pericytes efficiently take up and degrade α-syn through the lysosomal pathway but not the ubiquitin-proteasome system. Furthermore, when pericytes were exposed the ubiquitin proteasome inhibitor-MG132 and α-syn aggregates, there was profound cytotoxicity through the production of reactive oxygen species resulting in apoptosis. These results suggest that the observed accumulation of α-syn in pericytes in human PD brains likely plays a role in PD pathogenesis, perhaps by causing cerebrovascular instability, under conditions of cellular stress.
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