Title:Anticancer Mammalian Target of Rapamycin (mTOR) Signaling Pathway Inhibitors: Current Status, Challenges and Future Prospects in Management of Epilepsy
Volume: 15
Issue: 8
Author(s): Arindam Ghosh Mazumder, Yogendra Shantaram Padwad and Damanpreet Singh
Affiliation:
Keywords:
Epilepsy, hippocampus, mossy fiber sprouting, rapamycin, traumatic brain injury, tuberous sclerosis complex.
Abstract: The role of phosphatidylinositol 3-kinase linked mammalian target of
rapamycin (mTOR) pathway hyperactivation is well established in cancer
pathogenesis. Several molecules inhibiting mTOR pathway, leading to inhibition of
protein synthesis responsible for angiogenesis of tumor cells have emerged out to be
potential anticancers. Similar hyperactivation of mTOR pathway has also reported in
epilepsy during latent phase, following precipitating injury causing reorganization of
neuronal networks and ultimately leading to induction of seizures. The mTOR
inhibitors have also found to attenuate pathological changes in the brain associated
with epilepsy, primarily suppression of mossy fiber sprouting. At the same time, a
few antiepileptic molecules which have been studied against cancer showed
anticancer activity, apart from their principal mechanism of action. These studies suggest mTOR
signaling pathway to be a common pathogenic link between cancer and epilepsy. It has been found that,
anticancer molecules acting on different molecular targets, that ultimately down regulate the expression
of mTOR, can also be used in case of epilepsy to reduce its hyperactivation. There are several
unexplored anticancer molecules that act by inhibiting mTOR directly or indirectly available which can
be explored as antiepileptic in future. Majority of the molecules which are tested as anticancer do not
reach the final phases of clinical trials due to less potency and efficacy, and ultimately a few of them
reach the market. Since a lot of experimental/safety studies have already been conducted on such
molecules, hence it is worthwhile to test these molecules for other disorders that share common
pathogenic pathway like epilepsy, provided their pitfalls have been addressed, as proposed in the
present review.
