Mortiboys, H., MacDonald, R., Payne, T. et al. (3 more authors) (2018) Translational approaches to restoring mitochondrial function in Parkinson's disease. FEBS Letters, 592 (5). pp. 776-792. ISSN 0014-5793
Abstract
There is strong evidence of a key role for mitochondrial dysfunction in both sporadic and all forms of familial Parkinson's disease (PD). However, none of the clinical trials carried out with putative mitochondrial rescue agents has been successful. Firm establishment of a wet biomarker or a reliable readout from imaging studies detecting mitochondrial dysfunction and reflecting disease progression is also awaited. We will provide an overview of our current knowledge about mitochondrial dysfunction in PD and related drug screens. We will also summarize previously undertaken mitochondrial wet biomarker studies and relevant imaging studies with particular focus on 31P-MRI Spectroscopy. We will conclude with an overview of clinical trials which tested putative mitochondrial rescue agents in PD patients. Parkinson's disease is a common, relentlessly progressive neurodegenerative disorder. The pathological hallmark is loss of dopaminergic neurons in the substantia nigra. The resulting motor presentation includes rest tremor, bradykinesia and rigidity but the importance of non-motor symptoms such as cognitive impairment and depression is increasingly recognized, too. Currently available dopaminergic treatment often only addresses the motor impairment partially. This review will summarize our current knowledge about mitochondrial dysfunction as a key target for disease-modifying treatment for PD. We will also provide an update on mitochondrial readouts in PD patients, namely imaging and putative mitochondrial biomarkers, which may become highly relevant in the context of future drug trials. This article is protected by copyright. All rights reserved.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2017 Wiley. This is an author produced version of a paper subsequently published in FEBS Letters. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | mitochondria; neuroprotection; Parkinson's disease |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Neuroscience (Sheffield) The University of Sheffield > Sheffield Teaching Hospitals |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 30 Nov 2017 11:00 |
Last Modified: | 11 Apr 2024 11:20 |
Status: | Published |
Publisher: | Wiley |
Refereed: | Yes |
Identification Number: | 10.1002/1873-3468.12920 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:124689 |