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DOI

The risk of progression of most sporadic neurodegenerative diseases, including Alzheimer’s disease, increases with age. Traditionally, this is associated with a decrease in the efficiency of cell protection systems, in particular, molecular chaperones. Thus, the development of small molecules able to induce the synthesis of chaperones is a promising therapeutic approach to prevent neural diseases associated with ageing. Here, we describe a new compound IA-50, belonging to the class of indolylazines and featured by a low size of topological polar surface area, the property related to substances with potentially high membrane-penetrating activity. We also estimated the absorption, distribution, metabolism and excretion characteristics of IA-50 and found the substance to fit the effective drug criteria. The new compound was found to induce the synthesis and accumulation of Hsp70 in normal and aged neurons and in the hippocampi of young and old mice. The transgenic model of Alzheimer’s disease, based on 5xFAD mice, confirmed that the injection of IA-50 prevented the formation of β-amyloid aggregates, loss of hippocampal neurons and the development of memory impairment. These data indicate that this novel substance may induce the expression of chaperones in neural cells and brain tissues, suggesting its possible application in the therapy of ageing-associated disorders.
Язык оригиналаАнглийский
Номер статьи8950
ЖурналMolecules
Том27
Номер выпуска24
DOI
СостояниеОпубликовано - 2022

    Предметные области WoS

  • Биохимия и молекулярная биология
  • Химия, Междисциплинарные труды

    Предметные области ASJC Scopus

  • Molecular Medicine
  • Chemistry (miscellaneous)
  • Analytical Chemistry
  • Organic Chemistry
  • Physical and Theoretical Chemistry
  • Medicine(all)
  • Drug Discovery
  • Pharmaceutical Science

ID: 33230040