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mTORC and PKCε in Regulation of Alcohol Use Disorder

Author(s):

Athirah Hanim, Isa Naina Mohamed, Rashidi M. Pakri Mohamed, Srijit Das, Norefrina Shafinaz Md Nor, Rosma Ayu Harun and Jaya Kumar*   Pages 1 - 14 ( 14 )

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 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 mTORC2 was recently reported to be associated with alcohol seeking behavior, suggesting the potential role of mTORC2-PKCε interactions in pathophysiology of AUD. Mammalian target to rapamycin complex 1 (mTORC1), another form of mTOR complex 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 pathogenesis of AUD.

Keywords:

mTORC1, mTORC2, PDK-1, PKCε, alcohol use disorder.

Affiliation:

Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, 56000 Cheras, Kuala Lumpur, Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, 56000 Cheras, Kuala Lumpur, Department of Family Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, 56000 Cheras, Kuala Lumpur, Department of Anatomy, Faculty of Medicine, Universiti Kebangsaan Malaysia, 56000 Cheras, Kuala Lumpur, Center of Neotechnology and Funtional Food, Faculty of Science and Technology, Universiti Kebangsaan, Faculty of Medicine, Universiti Kebangsaan Malaysia, 56000 Cheras, Kuala Lumpur, Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, 56000 Cheras, Kuala Lumpur



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