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Mitochondrial Permeability Transition: A Molecular Lesion with Multiple Drug Targets

Briston, T; Selwood, DL; Szabadkai, G; Duchen, MR; (2019) Mitochondrial Permeability Transition: A Molecular Lesion with Multiple Drug Targets. [Review]. Trends in Pharmacological Sciences , 40 (1) pp. 50-70. 10.1016/j.tips.2018.11.004. Green open access

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Abstract

Mitochondrial permeability transition, as the consequence of opening of a mitochondrial permeability transition pore (mPTP), is a cellular catastrophe. Initiating bioenergetic collapse and cell death, it has been implicated in the pathophysiology of major human diseases, including neuromuscular diseases of childhood, ischaemia-reperfusion injury, and age-related neurodegenerative disease. Opening of the mPTP represents a major therapeutic target, as it can be mitigated by a number of compounds. However, clinical studies have so far been disappointing. We therefore address the prospects and challenges faced in translating in vitro findings to clinical benefit. We review the role of mPTP opening in disease, discuss recent findings defining the putative structure of the mPTP, and explore strategies to identify novel, clinically useful mPTP inhibitors, highlighting key considerations in the drug discovery process.

Type: Article
Title: Mitochondrial Permeability Transition: A Molecular Lesion with Multiple Drug Targets
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.tips.2018.11.004
Publisher version: http://doi.org/10.1016/j.tips.2018.11.004
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: mitochondria, mPTP, cyclophilin D, drug discovery, calcium
UCL classification: UCL
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 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
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Wolfson Inst for Biomedical Research
URI: https://discovery.ucl.ac.uk/id/eprint/10065055
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