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.
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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.
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