Human pericytes degrade diverse α-synuclein aggregates

Birger Victor Dieriks (1) , Blake Highet (1) , Ania Alik (2, 3) , Tracy Bellande (2, 3) , Taylor J Stevenson (1) , Victoria Low (1) , Thomas I. H. Park (1) , Jason Correia (1, 4) , Patrick Schweder (1) , Richard L M Faull (1) , Ronald Melki (2, 3) , Maurice A Curtis (1) , Mike Dragunow (1)

1 University of Auckland [Auckland]
2 JACOB - Institut de Biologie François JACOB
3 LMN - Laboratoire des Maladies Neurodégénératives - UMR 9199
4 Auckland City Hospital

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.

Domaines: Neurobiologie

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⟩