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Chaperone-mediated autophagy as a therapeutic target for Parkinson disease

Campbell, P; Morris, H; Schapira, A; (2018) Chaperone-mediated autophagy as a therapeutic target for Parkinson disease. Expert Opinion on Therapeutic Targets , 22 (10) pp. 823-832. 10.1080/14728222.2018.1517156. Green open access

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Abstract

INTRODUCTION: Parkinson disease (PD) is the most common neurodegenerative movement disorder. Currently only symptomatic treatments exist for PD, and so the search for potential neuroprotective drug targets is of great importance. Chaperone mediated autophagy (CMA) is one of the key cellular mechanisms in protein homeostasis. Many of the pathogenic pathways thought to be important in PD converge on CMA, thus rendering it an attractive therapeutic target. Areas covered: In this review we discuss current up-to-date knowledge of the molecular mechanisms involved in CMA function and regulation. We go on to discuss the links between CMA and PD including CMA's role in ɑ-synuclein processing, oxidative stress, and mitochondrial function. We finish by exploring the potential benefits of how upregulation of CMA may be beneficial in PD and strategies to achieve this. Expert opinion: Upregulation of CMA is an attractive therapeutic target in PD due to its links with several pathogenic pathways . Currently more knowledge of the mechanisms that regulate CMA is required to allow for the development of specific CMA modulators. However, recent studies demonstrating the role of retinoic acid derivatives and miRNAs in regulating CMA are promising, and indirect upregulation of CMA by modulating other lysosomal pathways may be helpful.

Type: Article
Title: Chaperone-mediated autophagy as a therapeutic target for Parkinson disease
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1080/14728222.2018.1517156
Publisher version: https://doi.org/10.1080/14728222.2018.1517156
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Chaperone-mediated autophagy, Parkinson disease, lysosome, mitochondrial function, proteostasis, therapeutics, ɑ-synuclein
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
URI: http://discovery.ucl.ac.uk/id/eprint/10057979
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