Modulation of Leucine Sensors to Mitigate Antipsychotics-Induced Metabolic Syndrome: A New Vista

TY - JOUR

T1 - Modulation of Leucine Sensors to Mitigate Antipsychotics-Induced Metabolic Syndrome

T2 - A New Vista

AU - Arjmand, Shokouh

AU - Biojone, Caroline

AU - Wegener, Gregers

PY - 2024/1/12

Y1 - 2024/1/12

N2 - Second-generation antipsychotics (SGAs) are currently the mainstay in the pharmacotherapy of some psychiatric disorders, which have improved the quality of life of millions of patients globally. A broad spectrum of activity and diminished liabilities of extrapyramidal side effects have made SGAs better alternatives compared to first-generation antipsychotics. Nevertheless, they display a complex profile of activity by affecting an array of biological targets and, as a result, are associated with a constellation of metabolic abnormalities such as hyperglycemia, dyslipidemia, weight gain, and cardiovascular problems. The SGAs-induced metabolic syndrome’s exact mechanism has remained nebulous, but some evidence points the finger at mTOR signaling. In this viewpoint, we propose potential strategies to prevent or alleviate the SGA-induced metabolic adverse effects by modulating the activity of the leucine sensors, Sestrins.

AB - Second-generation antipsychotics (SGAs) are currently the mainstay in the pharmacotherapy of some psychiatric disorders, which have improved the quality of life of millions of patients globally. A broad spectrum of activity and diminished liabilities of extrapyramidal side effects have made SGAs better alternatives compared to first-generation antipsychotics. Nevertheless, they display a complex profile of activity by affecting an array of biological targets and, as a result, are associated with a constellation of metabolic abnormalities such as hyperglycemia, dyslipidemia, weight gain, and cardiovascular problems. The SGAs-induced metabolic syndrome’s exact mechanism has remained nebulous, but some evidence points the finger at mTOR signaling. In this viewpoint, we propose potential strategies to prevent or alleviate the SGA-induced metabolic adverse effects by modulating the activity of the leucine sensors, Sestrins.

KW - Sestrins

KW - leucine

KW - mTORC

KW - metabolic syndrome

KW - second-generation antipsychotics

U2 - 10.1021/acsptsci.3c00319

DO - 10.1021/acsptsci.3c00319

M3 - Review

C2 - 38230284

SN - 2575-9108

VL - 7

SP - 294

EP - 297

JO - ACS Pharmacology and Translational Science

JF - ACS Pharmacology and Translational Science

IS - 1

ER -