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Neuroprotective and cognitive benefits of Semaglutide: Insights into the underlying molecular mechanisms
(Pergamon-Elsevier Science Ltd, 2025) Yaghmayee, Shayan; Moazzeni, Atefeh Sadat; Jamialahmadi, Tannaz; Karav, Sercan; Yaribeygi, Habib; Kesharwani, Prashant; Sahebkar, Amirhossein
Neuronal injury is a common complication in patients with diabetes. These injuries include a wide range of neurobehavioral complications that significantly reduce the neuronal network efficiency and quality of life in affected individuals. Currently, diabetes-induced neuronal complications are a major global health challenge, and many studies have been performed to prevent or slow their progression. Semaglutide is a novel form of glucagon-like peptide-1 (GLP-1) agonist agents that has recently been approved for diabetic patients to normalize glucose metabolism. However, some evidence indicates that it has extra-glycemic effects in some tissues as well as in the central nervous system. This evidence suggests that semaglutide can suppress some pathophysiological pathways involved in diabetes-induced neuronal complications and thus improve neuronal network efficiency. However, there is limited evidence to support all the pathways involved in mediating these benefits. In the current review, we aim to present the latest clinical and experimental findings on the possible benefits of semaglutide on major neuronal complications and to determine the possible molecular mechanisms involved.