PINK1 modulators as novel treatments for Parkinson’s Disease

Lambourne, Olivia 2021. PINK1 modulators as novel treatments for Parkinson’s Disease. PhD Thesis, Cardiff University. Item availability restricted.

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Abstract

Since the discovery that loss-of-function mutations in PINK1 result in early onset Parkinson’s disease (PD), there has been growing interest in the development of PINK1 activators as potential PD treatments. PINK1 is a serine/threonine kinase that is responsible for stimulating the autophagic removal of toxic, depolarised mitochondria through a process called mitophagy. Mitophagy occurs in many cells including dopaminergic neurons and therefore it has been proposed that by activating PINK1-dependent mitophagy, it would minimise oxidative stress and in turn prevent the loss of dopaminergic neurons that is characteristic of PD. This thesis focused on the design, synthesis and in vitro evaluation of a series of small molecules as PINK1 activators. A few hit compounds were identified that were more potent and less cytotoxic than the reported PINK1 activators. Furthermore, a novel prodrug strategy was designed and synthesised with the aim of selectively delivering the PINK1 activators to the mitochondria.

Item Type:	Thesis (PhD)
Date Type:	Completion
Status:	Unpublished
Schools:	Pharmacy
Subjects:	Q Science > Q Science (General)
Date of First Compliant Deposit:	12 May 2021
Last Modified:	30 Oct 2021 01:07
URI:	https://orca.cardiff.ac.uk/id/eprint/141194

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