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Journal Articles PLoS ONE Year : 2022

Human pericytes degrade diverse α-synuclein aggregates

Abstract

Parkinson's disease (PD) is a progressive, neurodegenerative disorder characterised by the abnormal accumulation of α-synuclein (α-syn) aggregates. Central to disease progression is the gradual spread of pathological α-syn. α-syn aggregation is closely linked to progressive neuron loss. As such, clearance of α-syn aggregates may slow the progression of PD and lead to less severe symptoms. Evidence is increasing that non-neuronal cells play a role in PD and other synucleinopathies such as Lewy body dementia and multiple system atrophy. Our previous work has shown that pericytes-vascular mural cells that regulate the blood-brain barrier-contain α-syn aggregates in human PD brains. Here, we demonstrate that pericytes efficiently internalise fibrillar α-syn irrespective of being in a monoculture or mixed neuronal cell culture. Pericytes cleave fibrillar α-syn aggregates (Fibrils, Ribbons, fibrils65, fibrils91 and fibrils110), with cleaved α-syn remaining present for up to 21 days. The number of α-syn aggregates/cell and average aggregate size depends on the type of strain, but differences disappear within 5 five hours of treatment. Our results highlight the role brain vasculature may play in reducing α-syn aggregate burden in PD.

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Neurobiology
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cea-03862437 , version 1 (21-11-2022)

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Birger Victor Dieriks, Blake Highet, Ania Alik, Tracy Bellande, Taylor J Stevenson, et al.. Human pericytes degrade diverse α-synuclein aggregates. PLoS ONE, 2022, 17 (11), pp.e0277658. ⟨10.1371/journal.pone.0277658⟩. ⟨cea-03862437⟩
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