The Role of the Gut in the Pathogenesis of Parkinson’s Disease: from Human Genetics to Epithelial α-Synuclein

Anastazja Gorecki

doi:10.26182/n9vd-g109

The Role of the Gut in the Pathogenesis of Parkinson’s Disease: from Human Genetics to Epithelial α-Synuclein

Anastazja Gorecki

School of Biological Sciences

Research output: Thesis › Doctoral Thesis

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Abstract

Parkinson’s disease (PD) is a neurological disorder linked to gut dysfunction, inflammation and microbial dysbiosis. Despite being an important regulator of gut homeostasis and host-microbe interactions, the intestinal barrier is neglected in PD research. This thesis used various techniques to investigate the contribution of the gut to PD, focussing on epithelial α-synuclein. Taken together, the results of this thesis: 1) demonstrate that PD risk is modulated by genetic variants regulating host microbe interactions at the gut barrier; 2) further characterise α-synuclein in gastrointestinal epithelial cell populations and 3) highlight a potential therapeutic which can mitigate α-synuclein pathology in the gut.

Original language	English
Qualification	Doctor of Philosophy
Awarding Institution	The University of Western Australia
Supervisors/Advisors	Rodger, Jennifer, Supervisor Dunlop, Sarah, Supervisor Kulkarni , Subhash, Supervisor, External person Anderton, Ryan, Supervisor, External person
Thesis sponsors	Australian Government Research Training Program
Award date	26 Jun 2023
DOIs	https://doi.org/10.26182/n9vd-g109
Publication status	Unpublished - 2023

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.26182/n9vd-g109

THESIS - DOCTOR OF PHILOSOPHY - GORECKI Anastazja Magda - 2023
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1 Article
1 Editorial
1 Review article

TLR2 and TLR4 in Parkinson’s disease pathogenesis: the environment takes a toll on the gut
Gorecki, A. M., Anyaegbu, C. C. & Anderton, R. S., Dec 2021, In: Translational Neurodegeneration. 10, 1, 47.
Research output: Contribution to journal › Review article › peer-review

Open Access

28 Citations (Scopus)
Single Nucleotide Polymorphisms Associated With Gut Homeostasis Influence Risk and Age-at-Onset of Parkinson's Disease
Gorecki, A. M., Bakeberg, M. C., Theunissen, F., Kenna, J., Hoes, M., Pfaff, A., Akkari, A., Dunlop, S., Koks, S., Mastaglia, F. & Anderton, R., 17 Nov 2020, In: Frontiers in Aging Neuroscience. 12, 603849.
Research output: Contribution to journal › Article › peer-review

Open Access

12 Citations (Scopus)
The gut-brain axis and gut inflammation in Parkinson’s disease: stopping neurodegeneration at the toll gate
Gorecki, A. M., Dunlop, S. A., Rodger, J. & Anderton, R. S., 2 Jul 2020, In: Expert Opinion on Therapeutic Targets. 24, 7, p. 601-604 4 p.
Research output: Contribution to journal › Editorial › peer-review

Open Access

10 Citations (Web of Science)

Cite this

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title = "The Role of the Gut in the Pathogenesis of Parkinson{\textquoteright}s Disease: from Human Genetics to Epithelial α-Synuclein",

abstract = "Parkinson{\textquoteright}s disease (PD) is a neurological disorder linked to gut dysfunction, inflammation and microbial dysbiosis. Despite being an important regulator of gut homeostasis and host-microbe interactions, the intestinal barrier is neglected in PD research. This thesis used various techniques to investigate the contribution of the gut to PD, focussing on epithelial α-synuclein. Taken together, the results of this thesis: 1) demonstrate that PD risk is modulated by genetic variants regulating host microbe interactions at the gut barrier; 2) further characterise α-synuclein in gastrointestinal epithelial cell populations and 3) highlight a potential therapeutic which can mitigate α-synuclein pathology in the gut.",

keywords = "α-synuclein, enteroendocrine cells, gut epithelium, Parkinson's disease, gut-brain axis, gut inflammation",

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AB - Parkinson’s disease (PD) is a neurological disorder linked to gut dysfunction, inflammation and microbial dysbiosis. Despite being an important regulator of gut homeostasis and host-microbe interactions, the intestinal barrier is neglected in PD research. This thesis used various techniques to investigate the contribution of the gut to PD, focussing on epithelial α-synuclein. Taken together, the results of this thesis: 1) demonstrate that PD risk is modulated by genetic variants regulating host microbe interactions at the gut barrier; 2) further characterise α-synuclein in gastrointestinal epithelial cell populations and 3) highlight a potential therapeutic which can mitigate α-synuclein pathology in the gut.

KW - α-synuclein

KW - enteroendocrine cells

KW - gut epithelium

KW - Parkinson's disease

KW - gut-brain axis

KW - gut inflammation

U2 - 10.26182/n9vd-g109

DO - 10.26182/n9vd-g109

M3 - Doctoral Thesis

ER -

The Role of the Gut in the Pathogenesis of Parkinson’s Disease: from Human Genetics to Epithelial α-Synuclein

Abstract

UN SDGs

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Research output

TLR2 and TLR4 in Parkinson’s disease pathogenesis: the environment takes a toll on the gut

Single Nucleotide Polymorphisms Associated With Gut Homeostasis Influence Risk and Age-at-Onset of Parkinson's Disease

The gut-brain axis and gut inflammation in Parkinson’s disease: stopping neurodegeneration at the toll gate

Cite this