α-Synuclein uptake, accumulation, and inflammatory responses in Parkinson’s disease

Show simple item record

dc.contributor.advisor Curtis, Maurice
dc.contributor.advisor Dragunow, Mike
dc.contributor.advisor Dieriks, Victor
dc.contributor.author Stevenson, Taylor J.
dc.date.accessioned 2022-01-06T02:56:56Z
dc.date.available 2022-01-06T02:56:56Z
dc.date.issued 2021 en
dc.identifier.uri https://hdl.handle.net/2292/57881
dc.description.abstract The misfolded protein α-synuclein is integral to the pathogenesis of Parkinson’s disease, leading to the death of dopaminergic neurons in the substantia nigra and resulting in the development of motor symptoms. Parkinson’s disease is usually considered a disease of neurons, however, non-neuronal cells could also be affected but have not been extensively studied. In this thesis, novel effects of α-synuclein in non-neuronal cells were investigated using human olfactory bulbs and in vitro cultures of pericytes and microglia derived from the human brain. Non-neuronal cells – pericytes, astrocytes and microglia contained α-synuclein in the Parkinson’s disease human olfactory bulb in similar numbers to neuronal cells. These findings were the basis for investigating the responses of primary human brain pericytes and microglia in vitro exposed to recombinant α-synuclein. This thesis demonstrates that α-synuclein does not induce inflammation in primary human brain pericytes and microglia except when it is heavily contaminated with bacterial endotoxins. Endotoxin-free α-synuclein did not induce inflammation in these cells. Additionally, primary human brain pericytes efficiently take up α-synuclein from the extracellular culture media, however, control and Parkinson’s disease autopsy post-mortem cells did not efficiently degrade the α-synuclein protein. Lastly, α-synuclein treatment alone did not induce cell death in primary human brain pericytes, however, treatment of pericytes with an additional stressor led to the induction of reactive oxygen species and subsequent cell death. These data suggest that non-neuronal cells are important in the pathogenesis of Parkinson’s disease and further understanding how they react to α-synuclein could provide new therapeutic approaches.
dc.publisher ResearchSpace@Auckland en
dc.relation.ispartof PhD Thesis - University of Auckland en
dc.relation.isreferencedby UoA en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated.
dc.rights.uri https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm en
dc.rights.uri http://creativecommons.org/licenses/by-nc-sa/3.0/nz/
dc.title α-Synuclein uptake, accumulation, and inflammatory responses in Parkinson’s disease
dc.type Thesis en
thesis.degree.discipline Anatomy
thesis.degree.grantor The University of Auckland en
thesis.degree.level Doctoral en
thesis.degree.name PhD en
dc.date.updated 2021-12-13T22:30:47Z
dc.rights.holder Copyright: The author en
dc.rights.accessrights http://purl.org/eprint/accessRights/OpenAccess en


Files in this item

Find Full text

This item appears in the following Collection(s)

Show simple item record

Share

Search ResearchSpace


Browse

Statistics