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REVIEW: Mitochondrial Disorders in Alzheimer’s Disease

Vladimir S. Sukhorukov1, Natalia M. Mudzhiri1,a*, Anastasia S. Voronkova1, Tatiana I. Baranich1,2, Valeria V. Glinkina2, and Sergey N. Illarioshkin1

1Research Center of Neurology, 125367 Moscow, Russia

2Pirogov Russian National Research Medical University (Pirogov Medical University), 117997 Moscow, Russia

* To whom correspondence should be addressed.

Received February 15, 2021; Revised February 15, 2021; Accepted March 23, 2021
Alzheimer’s disease is the most common age-related neurodegenerative disease. Understanding of its etiology and pathogenesis is constantly expanding. Thus, the increasing attention of researchers is directed to the study of the role of mitochondrial disorders. In addition, in recent years, the concept of Alzheimer’s disease as a stress-induced disease has begun to form more and more actively. The stress-induced damage to the neuronal system can trigger a vicious circle of pathological processes, among which mitochondrial dysfunctions have a significant place, since mitochondria represent a substantial component in the anti-stress activity of the cell. The study of mitochondrial disorders in Alzheimer’s disease is relevant for at least two reasons: first, as important pathogenetic component in this disease; second, due to vital role of mitochondria in formation of the body resistance to various conditions, including stressful ones, throughout the life. This literature review analyzes the results of a number of recent studies assessing potential significance of the mitochondrial disorders in Alzheimer’s disease. The probable mechanisms of mitochondrial disorders associated with the development of this disease are considered: bioenergetic dysfunctions, changes in mitochondrial DNA (including assessment of the significance of its haplogroup features), disorders in the dynamics of these organelles, oxidative damage to calcium channels, damage to MAM complexes (membranes associated with mitochondria; mitochondria-associated membranes), disruptions of the mitochondrial quality control system, mitochondrial permeability, etc. The issues of the “primary” or “secondary” mitochondrial damage in Alzheimer’s disease are discussed. Potentials for the development of new methods for diagnosis and therapy of mitochondrial disorders in Alzheimer’s disease are considered.
KEY WORDS: Alzheimer’s disease, stress-induced diseases, mitochondria, mitochondrial disorders

DOI: 10.1134/S0006297921060055