Mitochondria are an Important Target in the Search for new Drugs for the Treatment of Alzheimer′s Disease and Senile Dementia

  • E.F. Shevtsova Institute of Physiologically Active Compounds of the Russian Academy of Sciences, 1 Severny proezd, Moscow region, Chernogolovka, 142432 Russia
  • D.V. Vinogradova Institute of Physiologically Active Compounds of the Russian Academy of Sciences, 1 Severny proezd, Moscow region, Chernogolovka, 142432 Russia
  • M.E. Neganova Institute of Physiologically Active Compounds of the Russian Academy of Sciences, 1 Severny proezd, Moscow region, Chernogolovka, 142432 Russia
  • P.N. Shevtsov Institute of Physiologically Active Compounds of the Russian Academy of Sciences, 1 Severny proezd, Moscow region, Chernogolovka, 142432 Russia
  • B.V. Lednev Institute of Physiologically Active Compounds of the Russian Academy of Sciences, 1 Severny proezd, Moscow region, Chernogolovka, 142432 Russia
  • S.O. Bachurin Institute of Physiologically Active Compounds of the Russian Academy of Sciences, 1 Severny proezd, Moscow region, Chernogolovka, 142432 Russia
Keywords: neurodegenerative diseases, mitochondria, calcium, mitochondrial permeability transition pore, Dimebon

Abstract

The review and summarizes own and literature data about the role of mitochondria as the important target in the search for drugs for the treatment of neurodegenerative diseases. Aging is a major risk factor for sporadic forms of various neurodegenerative diseases, including Alzheimer′s disease. One of the most argued and currently accepted theories is the Mitochondrial Free Radical Theory of Aging. Mitochondrial hypotheses of the development of sporadic forms of neurodegenerative diseases particularly Alzheimer′s disease, are closely connected with it. Impairments of mitochondrial functions lead to a decrease in their ability to regulate calcium homeostasis in the cell and to a decrease in the threshold for the induction of mitochondrial permeability transition (MPT) pores. MPT inhibitors can be considered as a promising approach to the treatment of neurodegenerative diseases, since these drugs can not only exhibit the properties of neuroprotectors, but also can provide normalization of synaptic activity due to increased calcium capacity of mitochondria. The review presents data on the number of MPT inhibitors, including endogenous compounds melatonin and N-acetylserotonin, their bioisosteric analogue Dimebon and a number of other compounds. The use of mitochondria as a basis for the formation of screening strategy for the search for compounds for the treatment of neurodegenerative diseases is of particular interest – both as a test of their potential toxicity, and as a basis for the creation of metabolic stimulants and drugs with neuroprotective and cognitive-stimulating effect.

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Published
2018-09-10