Human pericytes degrade α-synuclein aggregates in a strain-dependent manner
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 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..
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Preprint| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
bioRxiv.org - (2022) vom: 13. Juni Zur Gesamtaufnahme - year:2022 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Dieriks, Birger Victor [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.1101/2022.06.08.495286 |
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| PPN (Katalog-ID): |
XBI036240443 |
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| 520 | |a 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 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. | ||
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| 700 | 1 | |a Alik, Ania |e verfasserin |4 aut | |
| 700 | 1 | |a Bellande, Tracy |e verfasserin |4 aut | |
| 700 | 1 | |a Stevenson, Taylor J. |e verfasserin |4 aut | |
| 700 | 1 | |a Low, Victoria |e verfasserin |4 aut | |
| 700 | 1 | |a Park, Thomas I-H |e verfasserin |4 aut | |
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