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Mini-Reviews in Medicinal Chemistry

Author(s): Athirah Hanim, Isa Naina Mohamed, Rashidi M. Pakri Mohamed, Srijit Das, Norefrina Shafinaz Md Nor, Rosma Ayu Harun and Jaya Kumar*

DOI: 10.2174/1389557520666200624122325

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mTORC and PKCε in Regulation of Alcohol Use Disorder

Page: [1696 - 1708] Pages: 13

  • * (Excluding Mailing and Handling)

Abstract

Alcohol use disorder (AUD) is characterized by compulsive binge alcohol intake, leading to various health and social harms. Protein Kinase C epsilon (PKCε), a specific family of PKC isoenzyme, regulates binge alcohol intake, and potentiates alcohol-related cues. Alcohol via upstream kinases like the mammalian target to rapamycin complex 1 (mTORC1) or 2 (mTORC2), may affect the activities of PKCε or vice versa in AUD. mTORC2 phosphorylates PKCε at hydrophobic and turn motif, and was recently reported to be associated with alcohol-seeking behavior, suggesting the potential role of mTORC2-PKCε interactions in the pathophysiology of AUD. mTORC1 regulates translation of synaptic proteins involved in alcohol-induced plasticity. Hence, in this article, we aimed to review the molecular composition of mTORC1 and mTORC2, drugs targeting PKCε, mTORC1, and mTORC2 in AUD, upstream regulation of mTORC1 and mTORC2 in AUD and downstream cellular mechanisms of mTORCs in the pathogenesis of AUD.

Keywords: mTORC1, mTORC2, PDK-1, PKCε, alcohol use disorder, epsilon, alcohol dependence, binge drinking.

Graphical Abstract

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