Cognitive dysfunction and metabolic comorbidities in mood disorders: A repurposing opportunity for glucagon-like peptide 1 receptor agonists?

Neuropharmacology
Rodrigo B MansurRoger S McIntyre

Abstract

Major depressive disorder and bipolar disorder are highly prevalent and disabling conditions. Cognition is considered a core domain of their psychopathology and a principle mediator of psychosocial impairment, disproportionately accounting for overall illness-associated costs. There are few interventions with replicated evidence of efficacy in treating cognitive deficits in mood disorders. Evidence also indicates that cognitive deficits are associated with obesity and involve significant impairment across multiple domains. Conversely, weight-loss interventions, such as physical exercise and bariatric surgery, have been shown to beneficially affect cognitive function. This convergent phenomenology suggests that currently available agents that target metabolic systems may also be capable of mitigating deficits in cognitive functions, and are, therefore, candidates for repurposing. The incretin glucagon-like peptide-1 (GLP-1) is a hormone secreted by intestinal epithelial cells. GLP-1 receptors (GLP-1R) are widely expressed in the central nervous system. Activation of GLP-1R leads to facilitation of glucose utilization and antiapoptotic effects in various organs. Pre-clinical trials have demonstrated significant neuroprotective ef...Continue Reading

Citations

Mar 2, 2019·Expert Opinion on Drug Discovery·Mar QuiñonesOmar Al-Massadi
Apr 26, 2019·Expert Review of Neurotherapeutics·Matthew J KnightBernhard T Baune
Apr 1, 2019·Inflammopharmacology·Anja DulliusMárcia Inês Goettert
May 5, 2021·The International Journal of Neuroscience·LongQing ZhangXueBi Tian
May 19, 2021·Pharmacological Reports : PR·Jan Detka, Katarzyna Głombik

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