Mitochondria are essential cytoplasmic organelles critical for cell survival and death. fission resulting in mitochondrial structural changes and dysfunction and cell damage. Attempts have been made to develop molecules to reduce mitochondrial AK-7 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 says of mammalian cells and discusses research aimed at developing therapies such as Mdivi Dynasore and P110 to prevent or to inhibit excessive mitochondrial fission. Introduction Several lines of evidence suggest that abnormal mitochondrial dynamics is usually associated with aging; with neurodegenerative diseases such as Alzheimer’s disease (AD) Parkinson’s disease (PD) Huntington’s disease (HD) multiple sclerosis and amyotrophic lateral sclerosis (ALS); and with several inherited mitochondrial diseases. Mitochondrial dynamics is the delicate balance between mitochondrial fission and mitochondrial fusion in mammalian cells including neurons. Mitochondrial fission involves the division or fragmentation of one healthy mitochondrion into 2 and mitochondrial fusion involves DUSP5 the integration of 2 mitochondria (healthy or defective) into one elongated one. Fission and fusion are essential processes that maintain mitochondrial structure size shape morphology number and distribution in mammalian cells including neurons. Mitochondria are synthesized in the soma and AK-7 travel along exons dendrites and synapses; and supply energy for many synaptic functions of neurons. In healthy neurons fission and fusion balance equally and maintain mitochondrial dynamics and distribution [1-2]. However in neurons that express mutant proteins – such as amyloid beta (in AD) [3-9] Tau (in AD) [10-14] mutant huntingtin or mutant Htt (in HD) [15-20] mutant SOD1 (in ALS) [21-22] and mutant LRRK2 [23] or mutant parkin or mutant DJ1 (in PD) [24] and overexpression of α-synuclein [25] — the balance of fission and fusionis altered leading to structural and functional abnormalities in the mitochondria and ultimately to neuronal damage. Abnormal mitochondrial dynamics is usually caused by an imbalance in highly conserved GTPase genes AK-7 which are essential for mitochondrial fission and fusion. GTPase genes – dynamin-related protein 1 (Drp1) fission 1 (Fis1) mitofusins 1 and 2 (Mfn1 Mfn2) and optic atrophy 1 (Opa1) – regulate maintain and remodel mammalian mitochondria [2]. Recent research has revealed that abnormal mitochondrial dynamics is an early event in several diseases that involve oxidative stress and mitochondrial dysfunction including AD [3-9 61 HD [15-20] PD [23-25] ALS [21-22] multiple sclerosis AK-7 [26-31] cancer [33-34] diabetes [35-39] obesity [40-41] and alcohol injury [42-46] (Fig 1). Extensive recent research has also revealed that increased mitochondrial fission is usually a key factor in mitochondrial dysfunction probably caused by mutant protein(s) interacting with Drp1 resulting in the initiation of abnormal mitochondrial fission. Recently some progress has been made in developing molecules that are capable of inhibiting excessive mitochondrial fragmentation in order to treat patients with neurodegenerative diseases. Physique 1 Illustration showing human diseases that are involved with oxidative stress/mitochondrial dysfunction and abnormal mitochondrial dynamics as an early event in the disease process. In research aimed at developing treatments for patients with neurological diseases progress – although limited – has recently been made in developing molecules that are capable of inhibiting increased mitochondrial fission. The purpose of this article is usually to summarize recent progress in the development of therapiesto reduce increased mitochondrial fission and to maintain balanced mitochondrial dynamics healthy mitochondrial function and normal neuronal activity in neurodegenerative diseases particularly in AD and HD. This article also highlights mechanisms of excessive mitochondrial fission in AD and HD and discusses molecules that have been found to inhibit mitochondrial fission and enhance neuronal function. Mitochondrial dynamics Mitochondria are cytoplasmic organelles – AK-7 bag-like structures found in eukaryotic cells. Mitochondria are present where multiple cellular processes occur including.