Early intrathecal infusion of everolimus restores cognitive function and mood in a murine model of Alzheimer's disease.

Early intrathecal infusion of everolimus restores cognitive function and mood in a murine model of Alzheimer's disease. Exp Neurol. 2018 Sep 19;: Authors: Cassano T, Magini A, Giovagnoli S, Polchi A, Calcagnini S, Pace L, Lavecchia MA, Scuderi C, Bronzuoli MR, Ruggeri L, Gentileschi MP, Romano A, Gaetani S, De Marco F, Emiliani C, Dolcetta D Abstract The discovery that mammalian target of rapamycin (mTOR) inhibition increases lifespan in mice and restores/delays many aging phenotypes has led to the identification of a novel potential therapeutic target for the treatment of Alzheimer's disease (AD). Among mTOR inhibitors, everolimus, which has been developed to improve the pharmacokinetic characteristics of rapamycin, has been extensively profiled in preclinical and clinical studies as anticancer and immunosuppressive agent, but no information is available about its potential effects on neurodegenerative disorders. Using a reliable mouse model of AD (3 × Tg-AD mice), we explored whether short-term treatment with everolimus injected directly into the brain by osmotic pumps was able to modify AD-like pathology with low impact on peripheral organs. We first established in non-transgenic mice the stability of everolimus at 37 °C in comparison with rapamycin and, then, evaluated its pharmacokinetics and pharmacodynamics profiles through either a single peripheral (i.p.) or central (i.c.v.) route of administration. Finally, 6-month-...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research