Alzheimer´s disease and aging: can mTOR inhibitors kill two birds with one drug? (23-05857S)

Basic informations

Investigator: RNDr. Karel Valeš, Ph.D.
Main recipient: University of Hradec Králové 
Co-recipient: National Institute of Mental Health (NIMH); Institute of Molecular Geneticsof the Czech Academy of Sciences
Research period: 1/1/2023 - 31/12/2025
Total budget: 10,904,000 CZK
NIMH budget: 3,527,000 CZK
Supported by: Czech Science Foundation (GAČR)

Annotation

Alzheimer ́s disease (AD) is currently incurable neurodegenerative condition and one of the greatest health-care challenges of the 21st century. However, in spite of large gains in our understanding of AD pathogenesis and how the disease is conceptualized, there are still striking gaps mainly in available therapy. Detailed analysis of AD brains demonstrated upregulation of mTOR signaling during the neurodegenerative development. Moreover, recent studies pointed out that mTOR inhibition by rapamycin eradicates cognitive deficit and reduces levels of Aβ in transgenic mouse model of AD. Therefore, within this project we would like to focus on design, synthesize and biological evaluation of novel centrally active mTOR inhibitors. Finally, in vivo experiments including toxicity evaluation, pharmacokinetics and behavioral tests of these compounds will reveal whether this approach might become a new promise for further preclinical research and, plausibly, for clinical practice in AD therapy.