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Impaired mitochondrial homeostasis and neurodegeneration: towards new therapeutic targets?

Corona, JC; Duchen, MR; (2015) Impaired mitochondrial homeostasis and neurodegeneration: towards new therapeutic targets? J Bioenerg Biomembr , 47 (1-2) 89 - 99. 10.1007/s10863-014-9576-6. Green open access

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Abstract

The sustained integrity of the mitochondrial population of a cell is critical for maintained cell health, and disruption of that integrity is linked strongly to human disease, especially to the neurodegenerative diseases. These are appalling diseases causing untold levels of suffering for which treatment is woefully inadequate. Understanding the mechanisms that disturb mitochondrial homeostasis may therefore prove key to identification of potential new therapeutic pathways. Mechanisms causing mitochondrial dysfunction include the acute catastrophic loss of function caused by opening of the mitochondrial permeability transition pore (mPTP), which collapses bioenergetic function and initiates cell death. This is best characterised in ischaemic reperfusion injury, although it may also contribute to a number of other diseases. More insidious disturbances of mitochondrial homeostasis may result from impaired balance in the pathways that promote mitochondrial repair (biogenesis) and pathways that remove dysfunctional mitochondria (mitophagy). Impaired coordination between these processes is emerging as a key feature of a number of neurodegenerative and neuromuscular disorders. Here we review pathways that may prove to be valuable potential therapeutic targets, focussing on the molecular mechanisms that govern the coordination of these processes and their involvement in neurodegenerative diseases.

Type: Article
Title: Impaired mitochondrial homeostasis and neurodegeneration: towards new therapeutic targets?
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1007/s10863-014-9576-6
Publisher version: http://dx.doi.org/10.1007/s10863-014-9576-6
Language: English
Additional information: © The Author(s) 2014. This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
UCL classification: UCL
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 Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
URI: https://discovery.ucl.ac.uk/id/eprint/1448926
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