Mitochondrial Permeability Transition: A Molecular Lesion with Multiple Drug Targets
| Autor: | Gyorgy Szabadkai, David L. Selwood, Thomas Briston, Michael R. Duchen |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Drug Programmed cell death media_common.quotation_subject Disease Mitochondrion Toxicology mPTP Mitochondrial Membrane Transport Proteins drug discovery 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Medicine Animals Humans cardiovascular diseases Molecular Targeted Therapy Child Molecular lesion media_common Pharmacology calcium Cell Death business.industry Drug discovery Mitochondrial Permeability Transition Pore cyclophilin D mitochondria Drug Discovery Mitochondria Neurodegenerative Diseases Neuromuscular Diseases Reperfusion Injury MPTP 030104 developmental biology chemistry Mitochondrial permeability transition pore business Neuroscience 030217 neurology & neurosurgery |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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