TY - JOUR
T1 - MTORC and PKCε in regulation of alcohol use disorder
AU - Hanim, Athirah
AU - Mohamed, Isa Naina
AU - Pakri Mohamed, Rashidi M.
AU - Das, Srijit
AU - Nor, Norefrina Shafinaz Md
AU - Harun, Rosma Ayu
AU - Kumar, Jaya
N1 - Publisher Copyright:
© 2020 Bentham Science Publishers.
PY - 2020
Y1 - 2020
N2 - 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 isoen-zyme, regulates binge alcohol intake, and potentiates alcohol-related cues. Alcohol via upstream kinas-es 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.
AB - 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 isoen-zyme, regulates binge alcohol intake, and potentiates alcohol-related cues. Alcohol via upstream kinas-es 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.
KW - Alcohol dependence
KW - Alcohol use disorder
KW - Binge drinking
KW - Epsilon
KW - MTORC1
KW - MTORC2
KW - PDK-1
KW - PKCε
UR - http://www.scopus.com/inward/record.url?scp=85090939158&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85090939158&partnerID=8YFLogxK
U2 - 10.2174/1389557520666200624122325
DO - 10.2174/1389557520666200624122325
M3 - Review article
C2 - 32579497
AN - SCOPUS:85090939158
SN - 1389-5575
VL - 20
SP - 1696
EP - 1708
JO - Mini-Reviews in Medicinal Chemistry
JF - Mini-Reviews in Medicinal Chemistry
IS - 17
ER -
