Effects of rapamycin and TOR on aging and memory: implications for Alzheimer’s disease

Abstract

Rapamycin is a macrolide immunosuppressant drug, originally used as an anti-fungal agent, which is widely used in transplantation medicine to prevent organ rejection. Target of rapamycin (TOR) is an evolutionarily conserved serine/threonine kinase with pleiotropic cellular functions, regulating processes such as growth and metabolism, cell survival, transcription and autophagy. TOR intervenes in two distinct enzymatic complexes with different functions, a rapamycin-sensitive complex TORC1 and a rapamycin-insensitive complex TORC2. Rapamycin has an inhibitory effect on TORC1 activity and it has been suggested to increase life span, an effect correlated with decreased protein biosynthesis and autophagy activation. In the CNS, rapamycin shows beneficial effects in neuronal survival and plasticity, thus contributing to memory improvement. In this review, evidence implying rapamycin and TOR in aging/life span extension and memory improvement will be discussed. Recent findings about the effects of rapamycin on Alzheimer's disease-associated neuropathology will be also discussed.