Zofia Chrienova, David Rysanek, Josef Novak, Pavla Vasicova, Patrik Oleksak, Rudolf Andrys, Adam Skarka, Jelena Dumanovic, Zoran Milovanovic, Vesna Jacevic, Marketa Chvojkova, Kristina Holubova, Karel Vales, Veronika Skoupilova, Marian Valko, Klaudia Jomova, Suliman Y Alomar, Fernanda D Botelho, Tanos C C Franca, Kamil Kuca, Zdenek Hodny, Eugenie Nepovimova
Frentizole is immunosuppressive drug with low acute toxicity and lifespan-prolonging effect. Recently, frentizole´s potential to disrupt toxic amyloid β (Aβ) - Aβ-binding alcohol dehydrogenase (ABAD) interaction in mitochondria in Alzheimer´s brains has been revealed. Another broadly studied drug with anti-aging and immunosuppressive properties is an mTOR inhibitor - rapamycin. Since we do not yet precisely know what is behind the lifespan-prolonging effect of rapamycin and frentizole, whether it is the ability to inhibit the mTOR signaling pathway, reduction in mitochondrial toxicity, immunosuppressive effect, or a combination of all of them, we have decided within our previous work to dock the entire in-house library of almost 240 Aβ-ABAD modulators into the FKBP-rapamycin-binding (FRB) domain of mTOR in order to interlink mTOR-centric and mitochondrial free radical-centric theories of aging and thus to increase the chances of success...
September 30, 2023: Biomedicine & Pharmacotherapy