Белки теплового шока при конформационных болезнях мозга

Abstract

An increase in the number of fatal chronic neurodegenerative diseases, in-cluding Parkinson’s disease, Alzheimer’s disease, Huntington’s chorea, amyotrophiclateral sclerosis, etc., is observed worldwide. These diseases are classified as conforma-tional diseases of the brain because the pathogenesis of this type of disease is a violationof the three-dimensional spatial folding of certain neuronal protein molecules, which isaccompanied by a change in the conformation of proteins, the formation of toxic oligo-mers and insoluble protein aggregates in affected cells. To maintain proteostasis and pre-vent the accumulation of potentially toxic protein aggregates, cells use interconnectedmolecular networks. This review presents current data on the organization of the proteo-stasis network, which includes mechanisms that control biogenesis, folding, transport,disaggregation, and degradation of proteins. The focus is on heat shock proteins of theHSP70 family and small chaperones sHSPs, which act as central coordinators of theproteostasis network. Clinical and morphological manifestations and pathogeneticmechanisms of the development of the most common conformational diseases of thebrain are reviewed, and recent data on the key role of the HSP70 chaperones and sHSPsin protecting cells against the consequences of improper folding and protein aggregationare presented. The main achievements of preclinical studies of currently known pharma-cological inductors of heat shock proteins in the neuroprotective therapy of conforma-tional diseases of the brain are reviewed.