dc.contributor.author |
Stevenson, Taylor J |
|
dc.contributor.author |
Johnson, Rebecca H |
|
dc.contributor.author |
Savistchenko, Jimmy |
|
dc.contributor.author |
Rustenhoven, Justin |
|
dc.contributor.author |
Woolf, Zoe |
|
dc.contributor.author |
Smyth, Leon CD |
|
dc.contributor.author |
Murray, Helen C |
|
dc.contributor.author |
Faull, Richard LM |
|
dc.contributor.author |
Correia, Jason |
|
dc.contributor.author |
Schweder, Patrick |
|
dc.contributor.author |
Heppner, Peter |
|
dc.contributor.author |
Turner, Clinton |
|
dc.contributor.author |
Melki, Ronald |
|
dc.contributor.author |
Dieriks, Birger V |
|
dc.contributor.author |
Curtis, Maurice A |
|
dc.contributor.author |
Dragunow, Michael |
|
dc.coverage.spatial |
England |
|
dc.date.accessioned |
2023-01-17T01:44:05Z |
|
dc.date.available |
2023-01-17T01:44:05Z |
|
dc.date.issued |
2022-10-15 |
|
dc.identifier.citation |
(2022). Scientific Reports, 12(1), 17314-. |
|
dc.identifier.issn |
2045-2322 |
|
dc.identifier.uri |
https://hdl.handle.net/2292/62394 |
|
dc.description.abstract |
Parkinson's disease (PD) is characterised by the progressive loss of midbrain dopaminergic neurons and the presence of aggregated α-synuclein (α-syn). Pericytes and microglia, two non-neuronal cells contain α-syn in the human brain, however, their role in disease processes is poorly understood. Pericytes, found surrounding the capillaries in the brain are important for maintaining the blood-brain barrier, controlling blood flow and mediating inflammation. In this study, primary human brain pericytes and microglia were exposed to two different α-synuclein aggregates. Inflammatory responses were assessed using immunocytochemistry, cytometric bead arrays and proteome profiler cytokine array kits. Fixed flow cytometry was used to investigate the uptake and subsequent degradation of α-syn in pericytes. We found that the two α-syn aggregates are devoid of inflammatory and cytotoxic actions on human brain derived pericytes and microglia. Although α-syn did not induce an inflammatory response, pericytes efficiently take up and degrade α-syn through the lysosomal pathway but not the ubiquitin-proteasome system. Furthermore, when pericytes were exposed the ubiquitin proteasome inhibitor-MG132 and α-syn aggregates, there was profound cytotoxicity through the production of reactive oxygen species resulting in apoptosis. These results suggest that the observed accumulation of α-syn in pericytes in human PD brains likely plays a role in PD pathogenesis, perhaps by causing cerebrovascular instability, under conditions of cellular stress. |
|
dc.format.medium |
Electronic |
|
dc.language |
eng |
|
dc.publisher |
Springer Nature |
|
dc.relation.ispartofseries |
Scientific reports |
|
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. |
|
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
|
dc.rights.uri |
http://creativecommons.org/licenses/by/4.0/ |
|
dc.subject |
Pericytes |
|
dc.subject |
Humans |
|
dc.subject |
Parkinson Disease |
|
dc.subject |
Reactive Oxygen Species |
|
dc.subject |
Proteasome Endopeptidase Complex |
|
dc.subject |
Proteome |
|
dc.subject |
Ubiquitin |
|
dc.subject |
Cytokines |
|
dc.subject |
Apoptosis |
|
dc.subject |
alpha-Synuclein |
|
dc.subject |
Proteasome Inhibitors |
|
dc.subject |
Brain Disorders |
|
dc.subject |
Neurosciences |
|
dc.subject |
Neurodegenerative |
|
dc.subject |
Stem Cell Research |
|
dc.subject |
Stem Cell Research - Nonembryonic - Human |
|
dc.subject |
Parkinson's Disease |
|
dc.subject |
2 Aetiology |
|
dc.subject |
1 Underpinning research |
|
dc.subject |
1.1 Normal biological development and functioning |
|
dc.subject |
2.1 Biological and endogenous factors |
|
dc.subject |
Neurological |
|
dc.title |
Pericytes take up and degrade α-synuclein but succumb to apoptosis under cellular stress. |
|
dc.type |
Journal Article |
|
dc.identifier.doi |
10.1038/s41598-022-20261-0 |
|
pubs.issue |
1 |
|
pubs.begin-page |
17314 |
|
pubs.volume |
12 |
|
dc.date.updated |
2022-12-02T20:52:02Z |
|
dc.rights.holder |
Copyright: The authors |
en |
dc.identifier.pmid |
36243723 (pubmed) |
|
pubs.author-url |
https://www.ncbi.nlm.nih.gov/pubmed/36243723 |
|
pubs.publication-status |
Published |
|
dc.rights.accessrights |
http://purl.org/eprint/accessRights/OpenAccess |
en |
pubs.subtype |
research-article |
|
pubs.subtype |
Journal Article |
|
pubs.elements-id |
922526 |
|
pubs.org-id |
Medical and Health Sciences |
|
pubs.org-id |
Medical Sciences |
|
pubs.org-id |
Anatomy and Medical Imaging |
|
pubs.org-id |
Pharmacology |
|
dc.identifier.eissn |
2045-2322 |
|
dc.identifier.pii |
10.1038/s41598-022-20261-0 |
|
pubs.number |
17314 |
|
pubs.record-created-at-source-date |
2022-12-03 |
|
pubs.online-publication-date |
2022-10-15 |
|