ALPHA- AND GAMMA-SYNUCLEINS CONTROL ENERGY METABOLISM AND ACTIVITY OF XANTHIN OXIDASE IN BRAIN CELLS

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Abstract

The process of transmission and transformation of signal in the central nervous system causes large energy expenditures in brain cells, which leads to active energy metabolism with high consumption of glucose and oxygen. Production of reactive oxygen species (ROS) as a result of these processes participate in signal transduction in the cell, but overproduction of ROS leads to the development of oxidative stress. Oxidative stress and aggregation of the α-synuclein is a hallmark in the mechanism of neuronal loss in Parkinson's disease. However, much less is known about the physiological role of monomeric synucleins. Using acute brain slices and primary neuroglial co-cultures prepared from transgenic mice with knockout of α-, β-, and γ-synuclein genes, we studied the role of these proteins in ROS production and energy metabolism. We found that synuclein knockout results in reduced ROS production compared to wild-type cells. Xanthine oxidase (XO) inhibitor oxypurinol reduced ROS production in wild-type cells and β-synuclein knockout brain slices, while XO-dependent ROS was not inhibited in α- or γ-synuclein knockout slices, suggesting that these proteins may regulate this enzyme. Knockout of α- and γ-synucleins resulted in a decrease in mitochondrial membrane potential and a reduction in energy capacity (in the form of ATP), which may be one of the mechanisms of XO regulation by synucleins.

About the authors

A. A Fedulina

Orel State University named after I.S. Turgenev; Lobachevsky State University of Nizhny Novgorod

Oryol, Russia; Nizhny Novgorod, Russia

E. S Seryogina

Orel State University named after I.S. Turgenev

Oryol, Russia

A. M Krayushkina

Institute of Physiologically Active Compounds at Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry RAS

Chernogolovka, Moscow Region, Russia

K. D Chaprov

Institute of Physiologically Active Compounds at Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry RAS

Chernogolovka, Moscow Region, Russia

A. Y Vinokurov

Orel State University named after I.S. Turgenev

Email: vinokurovayu@oreluniver.ru
Oryol, Russia

A. Y Abramov

Orel State University named after I.S. Turgenev; UCL Queen Square Institute of Neurology

Oryol, Russia; London, UK

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