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Developing a nanoplatform to prevent the spread of Parkinson's disease

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thesis
posted on 29.03.2022, 02:16 by India Jade Boyton
Parkinson's disease (PD) spreads in the brain via the release of the protein α-synuclein from diseased neurons into the extracellular space, where nearby healthy brain cells take it up, triggering misfolding and aggregation of α-synuclein in those cells. Thus, pathology spreads in the brain, leading to the symptoms of PD. The overarching aim of this project was to investigate the potential of a novel protein nanocage system for the targeted capture of abnormal α-synuclein, preventing its transmission between brain cells and halting PD progression. Encapsulin protein nanocages selectively self-assemble around proteins tagged with a unique encapsulation signal peptide (ESig), encapsulating them. To better understand this process, the biophysical mechanisms and physicochemical factors underlying encapsulin disassembly/reassembly was characterised using spectroscopic techniques. Encapsulin was found to reversibly disassemble in extreme guanidine hydrochloride (4-7 M) and alkaline conditions and then reassemble within 6-8 hours when returned to normal conditions. Encapsulin disassembly/reassembly conditions were optimised and applied to successfully capture untagged superfolder green fluorescent protein. These results will help pave the way towards the capture of untagged pathological α-synuclein, and the potential future development of a capture system that halts the progression of PD in in vitro models -- abstract.

History

Notes

Theoretical thesis. Bibliography: pages 59-62

Awarding Institution

Macquarie University

Degree Type

Thesis MRes

Degree

MRes, Macquarie University, Faculty of Science and Engineering, Department of Molecular Sciences

Department, Centre or School

Department of Molecular Sciences

Year of Award

2020

Principal Supervisor

Andrew Care

Additional Supervisor 1

Lyndsey Collins-Praino

Rights

Copyright India Jade Boyton 2020. Copyright disclaimer: http://mq.edu.au/library/copyright

Language

English

Extent

1 online resource (viii, 64 pages) graphs

Former Identifiers

mq:72387 http://hdl.handle.net/1959.14/1284353