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Human pericytes degrade diverse α-synuclein aggregates
Birger Victor Dieriks 1 2, Blake Highet 1 2, Ania Alik 3, Tracy Bellande 3, Taylor J Stevenson 1 2, Victoria Low 1 2, Thomas I-H Park 2 4, Jason Correia 2 5, Patrick Schweder 2 5, Richard L M Faull 1 2, Ronald Melki 3, Maurice A Curtis 1 2, Mike Dragunow 2 4
...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.