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mTOR as an eligible molecular target for possible pharmacological treatment of nonalcoholic steatohepatitis

Publication at First Faculty of Medicine |
2022

Abstract

Currently, non-alcoholic fatty liver disease (NAFLD) progressing into chronic non-alcoholic steatohepatitis (NASH), liver cirrhosis, and eventually hepatocellular cancer has emerged as an epidemiological concern due to lack of proven treatment. Our review briefly comprises of the mechanism of pathogenesis and inflammation corresponding to the disease, and all the offered insights of mechanistic pathways that could be targeted in the progression of NASH.

The review principally focuses on mTOR (mammalian target of rapamycin) as a promising target highlighting its immense role in lipogenesis and alleviating inflammation and fibrosis. A detailed description of signaling pathways of mTORC1 and mTORC2 that are inhibited by rapamycin and other mTOR inhibitor analogues is accentuated.

The exploration of mTOR inhibitors clearly explains the exigent molecular aspects of mTOR in regulating adipocyte and lipogenic marker genes (e.g. those encoding PPAR gamma, SREBP1c). The literature on available mTOR inhibitors and their classification so far could be extremely useful in highlighting mTOR as a favorable drug target in the indication of NASH in the near future.