title: Inhibitors of mitochondrial fission as a therapeutic strategy for diseases with oxidative stress and mitochondrial dysfunction.
abstract: Mitochondria are essential cytoplasmic organelles, critical for cell survival and death. Recent mitochondrial research revealed that mitochondrial dynamics-the balance of fission and fusion in normal mitochondrial dynamics--is an important cellular mechanism in eukaryotic cell and is involved in the maintenance of mitochondrial morphology, structure, number, distribution, and function. Research into mitochondria and cell function has revealed that mitochondrial dynamics is impaired in a large number of aging and neurodegenerative diseases, and in several inherited mitochondrial diseases, and that this impairment involves excessive mitochondrial fission, resulting in mitochondrial structural changes and dysfunction, and cell damage. Attempts have been made to develop molecules to reduce mitochondrial fission while maintaining normal mitochondrial fusion and function in those diseases that involve excessive mitochondrial fission. This review article discusses mechanisms of mitochondrial fission in normal and diseased states of mammalian cells and discusses research aimed at developing therapies, such as Mdivi, Dynasore and P110, to prevent or to inhibit excessive mitochondrial fission.
authors.affiliation: Neurogenetics Laboratory, Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR, USA Department of Physiology and Pharmacology, Oregon Health & Science University, Portland, OR, USA.
authors.forename: P Hemachandra
authors.initials: PH
authors.lastname: Reddy
mesh_terms: D000818:Animals; D006801:Humans; D006835:Hydrazones / Q000627:therapeutic use; D028361:Mitochondrial Diseases / Q000378:metabolism / Q000628:therapy*; D063154:Mitochondrial Dynamics / Q000187:drug effects / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000627:therapeutic use; D052999:Quinazolinones / Q000627:therapeutic use
chemical_list: C549041:3-(2,4-dichloro-5-methoxyphenyl)-2-sulfanyl-4(3H)-quinazolinone; D006835:Hydrazones; D024101:Mitochondrial Proteins; C511794:N'-(3,4-dihydroxybenzylidene)-3-hydroxy-2-naphthahydrazide; D052999:Quinazolinones; C037112:9-deoxy-delta-9-prostaglandin D2; D015230:Prostaglandin D2
keywords: Alzheimer's disease; fission inhibitors; free radical production; mitochondrial dynamics; mitochondrial dysfunction; oxidative stress