Aging is associated with a decline in cognitive function, which can partly be explained by the accumulation of damage to the brain cells over time. Neurons and glia undergo morphological and ultrastructure changes during aging. Over the past several years, it has become evident that at the cellular level, various hallmarks of an aging brain are closely related to mitophagy. The importance of mitochondria quality and quantity control through mitophagy is highlighted by the contribution that defects in mitochondria–autophagy crosstalk make to aging and age-related diseases. In this review, we analyze some of the more recent findings regarding the study of brain aging and neurodegeneration in the context of mitophagy. We discuss the data on the dynamics of selective autophagy in neurons and glial cells during aging and in the course of neurodegeneration, focusing on three mechanisms of mitophagy: non-receptor-mediated mitophagy, receptor-mediated mitophagy, and transcellular mitophagy. We review the role of mitophagy in neuronal/glial homeostasis and in the molecular pathogenesis of neurodegenerative disorders, such as Parkinson’s disease, Alzheimer’s disease, and other disorders. Common mechanisms of aging and neurodegeneration that are related to different mitophagy pathways provide a number of promising targets for potential therapeutic agents.

Mitochondrial dynamics significantly play a major role in the pathogenesis of neurodegenerative diseases, such as Parkinson’s disease and Alzheimer’s disease. The dysregulation of mitochondrial biogenesis and function, characterized by impaired fission and fusion processes mediated by a number of proteins, in particular, Drp1, Mfn1, Mfn2, Opa1, and PGC-1α, contributes to neuronal vulnerability and degeneration. Insufficient mitophagy and disrupted mitochondrial transport exacerbate oxidative stress and neurotoxicity. Emerging therapeutic strategies that target mitochondrial dynamics, including various pharmacological agents, demonstrate potential for restoring mitochondrial balance and enhancing neuroprotection. This growing body of research underscores the importance of mitochondrial health in developing effective interventions for neurodegenerative conditions. This review highlights well-established links between the disruption of mitochondrial dynamics and the development of neurodegenerative processes. We also discuss different therapeutic strategies that target mitochondrial function in neurons that have been proposed as perspective neuroprotective treatments.

There is growing evidence that the remodeling of cerebral microvessels plays an important role in plastic changes in the brain associated with development, experience, learning, and memory consolidation. At the same time, abnormal neoangiogenesis, and deregulated regulation of microvascular regression, or pruning, could contribute to the pathogenesis of neurodevelopmental diseases, stroke, and neurodegeneration. Aberrant remodeling of microvesselsis associated with blood–brain barrier breakdown, development of neuroinflammation, inadequate microcirculation in active brain regions, and leads to the dysfunction of the neurovascular unit and progressive neurological deficits. In this review, we summarize current data on the mechanisms of blood vessel regression and pruning in brain plasticity and in Alzheimer’s-type neurodegeneration. We discuss some novel approaches to modulating cerebral remodeling and preventing degeneration-coupled aberrant microvascular activity in chronic neurodegeneration.

Взаимодействию эндоплазматического ретикулума (ЭПР) и митохондрий до недавнего времени уделялось мало внимания. Однако за последние годы показано, что нарушение контактов между ЭПР и митохондриями является важным звеном этиопатогенеза таких нейродегенеративных заболеваний, как болезни Альцгеймера и Паркинсона, боковой амиотрофический склероз. В свете этих данных детальное изучение механизмов взаимодействия ЭПР с митохондриями необходимо для разработки новых подходов к диагностике и терапии нейродегенеративных и других заболеваний, а также для углубления фундаментальных знаний о физиологии эукариотической клетки в целом. В настоящем обзоре рассмотрена работа мембран ЭПР, ассоциированных с митохондриями. Проанализированы данные о структурных элементах системы этих мембран, ее вкладе в жизнедеятельность клетки (гомеостаз кальция, липидов, аутофагия, регуляция числа митохондрий, их слияние и деление), а также рассмотрена роль дисфункции ассоциированных с митохондриями мембран ЭПР в патогенезе различных заболеваний.

Accumulating data suggest that the brain undergoes various changes during aging. Among them are loss of both white and gray matter, neurons and synapses degeneration, as well as oxidative, inflammatory, and biochemical changes. The above-mentioned age-related features are closely related to autophagy and mitochondria. Therefore, we aimed to reveal the most peculiar morphological features of brain nervous tissue and to characterize the expression of autophagy and mitochondrial immunohistochemical biomarkers in neurons of different human brain zones during aging. Counting the number of neurons as well as Microtubule-associated proteins 1A/1B light chain 3B (LC3B), Heat shock protein 70 (HSP70), Lysosome-associated membrane protein type 2A (LAMP2A), Alpha subunit of ATP synthase (ATP5A), and Parkinson disease protein 7 (DJ1) immunohistochemical staining were performed on FFPE samples of human prefrontal cortex, corpus striatum, and hippocampus obtained from autopsy. Statistical analysis revealed a loss of neurons in the studied elderly group in comparison to the young group. When the expression of macroautophagy (LC3B), chaperon-mediated autophagy (HSP70, LAMP2A), and mitochondrial respiratory chain complex V (ATP5A) markers for the young and elderly groups were compared, the latter was found to have a significantly higher rate of optical density, whilst there was no significance in DJ1 expression. These findings, while preliminary, suggest that both autophagy and mitochondria are involved in neuronal maintenance during aging and could indicate their potential role in adaptive mechanisms that occur in aging.

In recent years, the dynamics of mitochondrial transformations in cells have been of more concern to both representatives of basic science and researchers in the field of applied medicine. A growing number of observations demonstrate the important regulatory influence of mitochondrial dynamics on a variety of physiological and pathological processes in many, if not all, organ and tissue structures. The prospects for studying the features and regulators of these processes for understanding the pathogenesis of diseases, developing their new biomarkers, as well as treatment technologies seem increasingly significant.   The purpose of this article is to review the facts obtained regarding mitochondrial dynamics, which, from the authors’ point of view, deserve the attention of pediatricians. The volume of relevant information turned out to be too extensive to fit into one article, which forced it to be divided into several successive publications. The first part provides information about the main processes included in the concept of “mitochondrial dynamics,” the importance of maintaining the balance of the latter for ontogenesis and tissue homeostasis, as well as data on its disturbances in diseases of the nervous system in children.