Heat Shock Proteins. Properties. Role in Adaptation. Methodological Approaches to Definition

The review presents the basic principles of personalized medicine in neurology, based on personified diagnostics, including approaches related to the analysis of the human genome, as well as the use of other omics technologies, such as neuroproteomics, neurometabolomics. The importance of taking into account the patient’s individual indicators (biomarkers) for the most accurate and timely diagnosis, monitoring the effectiveness and safety of therapy (theranostics) is discussed. Information on microRNAs with promising diagnostic potential is presented. The importance of pharmacogenomic studies for predicting the effectiveness of therapy is emphasized. The information on the study of the brain connectome and the mapping of the brain network is shown, which opens up new possibilities for understanding the physiological and pathological processes in the nervous system. The existing difficulties in the development of personalized medicine today are indicated and the undoubted benefits of individualized approaches in neurology are emphasized.

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Immunohistochemical Evaluation of Chaperone-Induced Autophagy in Various Parts of the Human Brain During Aging

Magnaeva,

Baranich,

Voronkov

et al. 2023

MorphoLetter

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Supporting of the functional pool of neurons during age-related brain involution is closely related to chaperone-mediated autophagy, the main function of which is to provide cellular proteostasis and utilize neurotoxic proteins. Impairment of this type of autophagy underlies the pathogenesis of many age-associated neurodegenerative diseases. In this aspect, it seems relevant to study the relationship between key markers of chaperone-mediated autophagy and their relative contribution to aging and neurodegeneration in order to determine pharmaceutical targets. The aim of the study was to determine the levels of expression of markers of chaperone-mediated autophagy - heat shock protein 70 (HSP70) and lysosome-associated membrane protein type 2A (LAMP2) in neurons of various areas of the human brain during aging. The study was performed on autopsy material of patients whose causes of death were not associated with neurological diseases. Preparations of the cortex of the precentral gyrus, striatum and hippocampus were studied in the group of cases of young age (35-45 years, n=5) and senile age (>75 years, n=10). Immunohistochemical staining was performed using primary antibodies to HSP70 and LAMP2. Optical density was assessed in the perikaryon of 150 large neurons in layer V of the cortex of the precentral gyrus, striatum, and pyramidal layer of the hippocampus. The results of the study demonstrated an increase in the expression of both HSP70 and LAMP2A in brain preparations from cases of senile age. The higher values of the optical density of HSP70 compared to LAMP2A in brain preparations from senile cases were probably due to dissociation between the stage of substrate binding and the stage of its translocation. It can be assumed that the binding of nonfunctioning proteins to HSP70 and cochaperones occurs faster than their movement into the lumen of lysosomes via LAMP2A. The results obtained suggest that the increasing of levels of markers of chaperone-mediated autophagy may be of a compensatory-adaptive nature and ensure the survival of neurons under conditions of chronic stress during physiological aging.

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Heat Shock Proteins. Properties. Role in Adaptation. Methodological Approaches to Definition

Cited by 5 publications

References 25 publications

Features of Changes in Exogenous Heat Shock Proteins (HSP 27 and HSP 70) in Patients with Occupational Nervous System Pathologies

Features of Changes in Exogenous Heat Shock Proteins (HSP 27 and HSP 70) in Patients with Occupational Nervous System Pathologies

Personalized neurology

Immunohistochemical Evaluation of Chaperone-Induced Autophagy in Various Parts of the Human Brain During Aging

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