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mTORC and PKCε in Regulation of Alcohol Use Disorder

[ Vol. 20 , Issue. 17 ]

Author(s):

Athirah Hanim, Isa Naina Mohamed, Rashidi M. Pakri Mohamed, Srijit Das, Norefrina Shafinaz Md Nor, Rosma Ayu Harun and Jaya Kumar*   Pages 1696 - 1708 ( 13 )

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.

Affiliation:

Department of Physiology, Faculty of Medicine, University Kebangsaan Malaysia, 56000 Cheras, Kuala Lumpur, Department of Pharmacology, Faculty of Medicine, University Kebangsaan Malaysia, 56000 Cheras, Kuala Lumpur, Department of Family Medicine, Faculty of Medicine, University Kebangsaan Malaysia, 56000 Cheras, Kuala Lumpur, Department of Anatomy, Faculty of Medicine, University Kebangsaan Malaysia, 56000 Cheras, Kuala Lumpur, Department of Biological Sciences and Biotechnology, Faculty of Science and Technology, University Kebangsaan Malaysia, 43600 Bangi, Selangor, Dean’s Office, Faculty of Medicine, University Kebangsaan Malaysia, 56000 Cheras, Kuala Lumpur, Department of Physiology, Faculty of Medicine, University Kebangsaan Malaysia, 56000 Cheras, Kuala Lumpur

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