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Abstract <p>Diabetes is one of the main risk factors for the developmentof cognitive dysfunction. Insulin resistance and chronic hyperglycemiacause a cascade of pathological events in the brain, including neuroinflammation,impaired neurotransmitter systems and energy metabolism, oxidativestress, and vascular pathologies that ultimately lead to neurodegeneration,loss of synaptic plasticity, brain aging, cognitive impairment,and dementia. The glucagon-like peptide (GLP–1) regulates food consumption andappetite, and its analogs, GLP-1 receptor agonists (GLP-1RAs), areused to treat type 2 diabetes, obesity, and metabolic syndrome.However, an increasing number of research studies are demonstrating thatthese substances also have neuroprotective effects in neurodegenerativediseases, mental disorders, and other brain conditions. Analysisof the effects of GLP-1 and GLP-1RAs on cognitive, psychometric, cellular,and molecular changes in preclinical and clinical studies showsthat these compounds and drugs modulate the molecular and cellularchanges that determine the phenomenology of many brain diseases. Byactivating GLP-1 receptors, natural GLP-1 and GLP-1RAs reduce insulinresistance, suppress neuroinflammation and oxidative stress, andprevent negative changes in neuroplasticity. The review considersthe repurposing of GLP-1Ras from the perspective of integrativephysiology, summarizes modern concepts about the mechanisms of actionof GLP-1RAs according to the results of experimental studies andpresents current clinical data on the use of GLP-1RAs in patientswith brain diseases. The use of GLP-1RA is a new therapeutic strategythat addresses both metabolic and cognitive/neuropsychiatric aspects,which is fundamentally important for the treatment of comorbid diseases.</p>

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Glucagon-Like Peptide-1 Receptor Agonists Are Promising for the Treatment of Brain Diseases: an Outlook from the Perspective of Integrative Physiology

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  • 发表日期：

    2025年10月1日

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  • N. V. Gulyaeva

摘要

Abstract

Diabetes is one of the main risk factors for the developmentof cognitive dysfunction. Insulin resistance and chronic hyperglycemiacause a cascade of pathological events in the brain, including neuroinflammation,impaired neurotransmitter systems and energy metabolism, oxidativestress, and vascular pathologies that ultimately lead to neurodegeneration,loss of synaptic plasticity, brain aging, cognitive impairment,and dementia. The glucagon-like peptide (GLP–1) regulates food consumption andappetite, and its analogs, GLP-1 receptor agonists (GLP-1RAs), areused to treat type 2 diabetes, obesity, and metabolic syndrome.However, an increasing number of research studies are demonstrating thatthese substances also have neuroprotective effects in neurodegenerativediseases, mental disorders, and other brain conditions. Analysisof the effects of GLP-1 and GLP-1RAs on cognitive, psychometric, cellular,and molecular changes in preclinical and clinical studies showsthat these compounds and drugs modulate the molecular and cellularchanges that determine the phenomenology of many brain diseases. Byactivating GLP-1 receptors, natural GLP-1 and GLP-1RAs reduce insulinresistance, suppress neuroinflammation and oxidative stress, andprevent negative changes in neuroplasticity. The review considersthe repurposing of GLP-1Ras from the perspective of integrativephysiology, summarizes modern concepts about the mechanisms of actionof GLP-1RAs according to the results of experimental studies andpresents current clinical data on the use of GLP-1RAs in patientswith brain diseases. The use of GLP-1RA is a new therapeutic strategythat addresses both metabolic and cognitive/neuropsychiatric aspects,which is fundamentally important for the treatment of comorbid diseases.