Promising horizon to alleviate Alzeheimer's disease pathological hallmarks via inhibiting mTOR signaling pathway: A new application for a commonplace analgesic.

Alzheimer's disease (AD) is a very prevalent and burdensome disease of elderlies but albeit extensive studies, mechanisms underlying its pathology and consequently its definite treatment is ambiguous. Intra and extra-cellular aggregation of abnormal proteins and impaired autophagy machinery, two closely related events taking place in AD brains proposed to be directly controlled by mTOR signaling pathway. On the other hand, tramadol that is a very well tolerated opioid analgesic has been revealed to inhibit mTOR upstream controllers through interaction with specific types of muscarinic, serotonergic, nicotinic and NMDA receptors, although it seems to induce the opposite effect via µ-opioid receptor. Putting all the pieces of experimental evidence together, we hypothesize that tramadol might alleviate AD pathological hallmarks at least in cellular level through decreasing activity of PI3K-AKT and ERK and also mTOR signaling pathways respectively and results in autophagy activation as well as tau-dephosphorylation.