Academic Journal
Glucagon-Like Peptide-1 Signaling in Learning and Memory: Evidence, Mechanisms, and Therapeutic Implications.
| Τίτλος: | Glucagon-Like Peptide-1 Signaling in Learning and Memory: Evidence, Mechanisms, and Therapeutic Implications. |
|---|---|
| Συγγραφείς: | Bashaw AG; Neuroscience Graduate Program, University of Southern California, Los Angeles, California., Roman-Ortiz C; Human and Evolutionary Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, California., Gao SX; Neuroscience Graduate Program, University of Southern California, Los Angeles, California., Schier LA; Neuroscience Graduate Program, University of Southern California, Los Angeles, California; Human and Evolutionary Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, California., Borner T; Neuroscience Graduate Program, University of Southern California, Los Angeles, California. Electronic address: tborner@usc.edu., Kanoski SE; Neuroscience Graduate Program, University of Southern California, Los Angeles, California; Human and Evolutionary Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, California. Electronic address: kanoski@usc.edu. |
| Πηγή: | Biological psychiatry [Biol Psychiatry] 2026 Oct 15; Vol. 100 (8), pp. 850-861. Date of Electronic Publication: 2026 Jun 19. |
| Τύπος έκδοσης: | Journal Article; Review |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Country of Publication: United States NLM ID: 0213264 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-2402 (Electronic) Linking ISSN: 00063223 NLM ISO Abbreviation: Biol Psychiatry Subsets: MEDLINE |
| Imprint Name(s): | Publication: New York, NY : Elsevier Original Publication: New York, Plenum Pub. Corp. |
| Ιατρικοί όροι (MeSH): | Memory*/physiology , Memory*/drug effects , Learning*/physiology , Learning*/drug effects , Glucagon-Like Peptide 1*/metabolism , Signal Transduction*/physiology , Glucagon-Like Peptide-1 Receptor*/metabolism , Hippocampus*/metabolism , Memory Disorders*/drug therapy , Memory Disorders*/metabolism, Humans ; Animals |
| Περίληψη: | Glucagon-like peptide-1 (GLP-1) is primarily known for its role in glucose homeostasis and food intake control, and GLP-1 analogs (either as monotherapy or dual agonists) are commonly used for type 2 diabetes and obesity treatment in humans. Beyond these functions, the GLP-1 receptor (GLP-1R) is widely expressed throughout the brain, including in the hippocampus (HPC) and interconnected regions that contribute to learning and memory processes. Here we review emerging evidence supporting a role for GLP-1 signaling in promoting learning and memory function, particularly in dementia and other conditions that manifest with HPC dysfunction. Evidence is synthesized from preclinical rodent models revealing that GLP-1 analog treatment improves deficits in memory function and HPC neuronal signaling processes in various models of dementia, aging, and metabolic disruption. While findings from human clinical trials and meta-analyses also show promise for GLP-1 analog-based treatment for memory disorders, results thus far are mixed, with many studies underpowered and/or lacking comprehensive memory evaluation. We describe several distinct yet non-mutually exclusive neurobiological mechanisms by which GLP-1R signaling can enhance memory, including blood-brain barrier penetration and direct action on HPC GLP-1Rs, improved peripheral and central insulin sensitivity, vagus nerve GLP-1R activation, and peripheral metabolic and inflammatory improvements. We conclude by emphasizing important considerations for future clinical trials for GLP-1 analogs in the treatment of Alzheimer's disease and other memory disorders, including focusing on metabolically vulnerable individuals, stratifying results by cardiovascular and metabolic status, and leveraging existing GLP-1 analogs and drug delivery approaches toward maximizing bioavailability and brain penetrance. (Copyright © 2026 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.) |
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| Grant Information: | F31 DK142526 United States DK NIDDK NIH HHS; R01 DC018562 United States DC NIDCD NIH HHS; R01 DK104897 United States DK NIDDK NIH HHS; R01 DK123423 United States DK NIDDK NIH HHS |
| Contributed Indexing: | Keywords: Alzheimer’s disease; Dementia; GLP-1; Hippocampus; Memory; Obesity |
| Substance Nomenclature: | 89750-14-1 (Glucagon-Like Peptide 1) 0 (Glucagon-Like Peptide-1 Receptor) |
| Entry Date(s): | Date Created: 20260619 Date Completed: 20260916 Latest Revision: 20260922 |
| Update Code: | 20260922 |
| PubMed Central ID: | PMC13587819 |
| DOI: | 10.1016/j.biopsych.2026.06.006 |
| PMID: | 42320781 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1873-2402 |
|---|---|
| DOI: | 10.1016/j.biopsych.2026.06.006 |