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Glucagon-Like Peptide-1 Signaling in Learning and Memory: Evidence, Mechanisms, and Therapeutic Implications.

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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
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  Data: Glucagon-Like Peptide-1 Signaling in Learning and Memory: Evidence, Mechanisms, and Therapeutic Implications.
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  Data: <searchLink fieldCode="AU" term="%22Bashaw+AG%22">Bashaw AG</searchLink>; Neuroscience Graduate Program, University of Southern California, Los Angeles, California.<br /><searchLink fieldCode="AU" term="%22Roman-Ortiz+C%22">Roman-Ortiz C</searchLink>; Human and Evolutionary Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, California.<br /><searchLink fieldCode="AU" term="%22Gao+SX%22">Gao SX</searchLink>; Neuroscience Graduate Program, University of Southern California, Los Angeles, California.<br /><searchLink fieldCode="AU" term="%22Schier+LA%22">Schier LA</searchLink>; 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.<br /><searchLink fieldCode="AU" term="%22Borner+T%22">Borner T</searchLink>; Neuroscience Graduate Program, University of Southern California, Los Angeles, California. Electronic address: tborner@usc.edu.<br /><searchLink fieldCode="AU" term="%22Kanoski+SE%22">Kanoski SE</searchLink>; 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.
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  Data: <searchLink fieldCode="JN" term="%220213264%22">Biological psychiatry</searchLink> [Biol Psychiatry] 2026 Oct 15; Vol. 100 (8), pp. 850-861. <i>Date of Electronic Publication: </i>2026 Jun 19.
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  Data: <searchLink fieldCode="MM" term="%22Memory%22">Memory*</searchLink>/<searchLink fieldCode="MM" term="%22Memory+physiology%22">physiology</searchLink> <br /><searchLink fieldCode="MM" term="%22Memory%22">Memory*</searchLink>/<searchLink fieldCode="MM" term="%22Memory+drug+effects%22">drug effects</searchLink> <br /><searchLink fieldCode="MM" term="%22Learning%22">Learning*</searchLink>/<searchLink fieldCode="MM" term="%22Learning+physiology%22">physiology</searchLink> <br /><searchLink fieldCode="MM" term="%22Learning%22">Learning*</searchLink>/<searchLink fieldCode="MM" term="%22Learning+drug+effects%22">drug effects</searchLink> <br /><searchLink fieldCode="MM" term="%22Glucagon-Like+Peptide+1%22">Glucagon-Like Peptide 1*</searchLink>/<searchLink fieldCode="MM" term="%22Glucagon-Like+Peptide+1+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Signal+Transduction%22">Signal Transduction*</searchLink>/<searchLink fieldCode="MM" term="%22Signal+Transduction+physiology%22">physiology</searchLink> <br /><searchLink fieldCode="MM" term="%22Glucagon-Like+Peptide-1+Receptor%22">Glucagon-Like Peptide-1 Receptor*</searchLink>/<searchLink fieldCode="MM" term="%22Glucagon-Like+Peptide-1+Receptor+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Hippocampus%22">Hippocampus*</searchLink>/<searchLink fieldCode="MM" term="%22Hippocampus+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Memory+Disorders%22">Memory Disorders*</searchLink>/<searchLink fieldCode="MM" term="%22Memory+Disorders+drug+therapy%22">drug therapy</searchLink> <br /><searchLink fieldCode="MM" term="%22Memory+Disorders%22">Memory Disorders*</searchLink>/<searchLink fieldCode="MM" term="%22Memory+Disorders+metabolism%22">metabolism</searchLink><br /><searchLink fieldCode="MH" term="%22Humans%22">Humans</searchLink> ; <searchLink fieldCode="MH" term="%22Animals%22">Animals</searchLink>
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  Data: 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.<br /> (Copyright © 2026 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)
– Name: Ref
  Label: References
  Group: RefInfo
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      – SubjectFull: Animals
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      – SubjectFull: Memory physiology
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      – SubjectFull: Learning physiology
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      – SubjectFull: Glucagon-Like Peptide 1 metabolism
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      – SubjectFull: Glucagon-Like Peptide-1 Receptor metabolism
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      – SubjectFull: Memory Disorders drug therapy
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      – SubjectFull: Memory Disorders metabolism
        Type: general
    Titles:
      – TitleFull: Glucagon-Like Peptide-1 Signaling in Learning and Memory: Evidence, Mechanisms, and Therapeutic Implications.
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      – PersonEntity:
          Name:
            NameFull: Borner T
      – PersonEntity:
          Name:
            NameFull: Kanoski SE
    IsPartOfRelationships:
      – BibEntity:
          Dates:
            – D: 15
              M: 10
              Text: 2026 Oct 15
              Type: published
              Y: 2026
          Identifiers:
            – Type: issn-electronic
              Value: 1873-2402
          Numbering:
            – Type: volume
              Value: 100
            – Type: issue
              Value: 8
          Titles:
            – TitleFull: Biological psychiatry
              Type: main
ResultId 1