RT Journal Article
SR Electronic
T1 Human pericytes degrade α-synuclein aggregates in a strain-dependent manner
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.06.08.495286
DO 10.1101/2022.06.08.495286
A1 Birger Victor Dieriks
A1 Blake Highet
A1 Ania Alik
A1 Tracy Bellande
A1 Taylor J. Stevenson
A1 Victoria Low
A1 Thomas I-H Park
A1 Jason Correia
A1 Patrick Schweder
A1 Richard L. M. Faull
A1 Ronald Melki
A1 Maurice A. Curtis
A1 Mike Dragunow
YR 2022
UL http://biorxiv.org/content/early/2022/06/10/2022.06.08.495286.abstract
AB 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 that non-neuronal cells play a role in PD and other synucleinopathies such as Lewy body dementia and multiple system atrophy are increasing. 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 efficiently break down α-syn aggregates in vitro, with clear differences in the number of α-syn aggregates/cell and average aggregate size when comparing five pure α-syn strains (Fibrils, Ribbons, fibrils65, fibrils91 and fibrils110). Furthermore, pericytes derived from PD brains have a less uniform response than those derived from control brains. Our results highlight the vital role brain vasculature may play in reducing α-syn burden in PD.