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Description
Agents, such as liraglutide and lixisenatide, have demonstrated effective central nervous system penetration, subsequently activating GLP-1 receptors and promoting neuroprotection and neuronal progenitor cell proliferation.120 Initial investigations into the neuroprotective effects of GLP-1RAs were conducted in diabetic animal models, where subcutaneous administration of liraglutide not only ameliorated hyperglycemia and peripheral insulin resistance, but also restored impaired brain insulin signaling, resulting in reduced tau hyperphosphorylation associated with AD pathology.121 Additionally, liraglutide enhanced learning and memory performance in diabetic mice.122 Notably, the beneficial effects of liraglutide on tau phosphorylation were not replicated by insulin therapy, suggesting that GLP-1RAs confer neuroprotection via mechanisms distinct from insulin signaling pathways.123 Following promising preclinical findings, several clinical trials have been initiated to evaluate the neuroprotective efficacy of GLP-1RAs in diverse populations, including individuals with diabetes, those at risk of cognitive decline, and patients diagnosed with AD or PD

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