Cited by 79Alzheimer's disease research and treatmentsDiabetes Treatment and ManagementNeuroinflammation and Neurodegeneration Mechanisms

Role of glucagon-like peptide-1 receptor agonists in Alzheimer’s disease and Parkinson’s disease

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Hong, Chien-Tai, Chen, Jia-Hung, Hu, Chaur-Jong·2024·Journal of Biomedical Science

Abstract

Neurodegenerative diseases, including Alzheimer's Disease (AD) and Parkinson's Disease (PD) are common complications of diabetes, arising from insulin resistance, inflammation, and other pathological processes in the central nervous system. The potential of numerous antidiabetic agents to modify neurodegenerative disease progression, both preclinically and clinically, has been assessed. These agents may provide additional therapeutic benefits beyond glycemic control. Introduced in the twenty-first century, glucagon-like peptide-1 receptor agonists (GLP-1RAs) are a class of antidiabetic drugs noted not only for their potent glucose-lowering effects but also for their cardiovascular and renal protective benefits. Various GLP-1RAs have been demonstrated to have significant benefits in in vitro and in vivo models of neurodegenerative diseases through modulating a variety of pathogenic mechanisms, including neuroinflammation, autophagy, mitochondrial dysfunction, and the abnormal phosphorylation of pathognomonic proteins. These agents also have substantial protective effects on cognitive and behavioral functions, such as motor function. However, clinical trials investigating GLP-1RAs in diseases such as AD, PD, mild cognitive impairment, psychiatric disorders, and diabetes have yielded mixed results for cognitive and motor function. This review examines the link between diabetes and neurodegenerative diseases, explores the effects of antidiabetic agents on neurodegeneration, provides a concise overview of the GLP-1 pathway, and discusses both preclinical and clinical trial outcomes of GLP-1RAs for neurodegenerative diseases, including their effects on cognition in AD and PD. This review also proposed new strategies for the design of future clinical trials on GLP-1 RAs for both AD and PD.

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  • Type 2 diabetes and obesity, characterized by insulin resistance, oxidative stress, and chronic inflammation, contribute to neurodegeneration.

    “These metabolic disorders, characterized by insulin resistance, oxidative stress, and chronic inflammation, contribute to neurodegeneration. 2”

    From Neurodegeneration and Stroke After Semaglutide and Tirzepatide in Patients With Diabetes and Obesity (2025) · cites this paper as [2]

    The “Diabetes and neurodegenerative diseases” section links diabetes to neurodegeneration through insulin resistance and inflammation; the figure caption in “Diabetes and pathogeneses of AD and PD” also identifies oxidative stress. These passages describe the mechanism as believed or postulated, and they do not establish the same claim for obesity. Page numbers are unavailable in our copy. (LLM, conf=0.86)

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Authors
Hong, C.-T., Chen, J.-H., & Hu, C.-J.
Affiliations
Taipei Medical University-Shuang Ho Hospital (TW)
Corresponding author
Hu, Chaur-Jong
Venue
Journal of Biomedical Science
Published
2024-11-05
Volume
31
Issue
1
Pages
102-102
ISSN
  • 1021-7770 (ISSN-L)
  • 1423-0127
OpenAlex
W4404054638
Cited by
78
References
108
Citations by year
2026: 42 · 2025: 34 · 2024: 2
FWCI
4.45
Type
journal article
Language
en
Open access
Locations
  • Journal of Biomedical Science (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
Ministry of Education (MOE) in Taiwan. (Higher Education Sprout Project)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
GLP-1 receptor agonists, Alzheimer's disease, Parkinson's disease, neurodegenerative diseases, diabetes mellitus, insulin resistance, neuroinflammation, autophagy, mitochondrial dysfunction, cognitive function, motor function, antidiabetic drugs, clinical trial design
MeSH terms
Glucagon-Like Peptide-1 Receptor, Glucagon-Like Peptide-1 Receptor Agonists, Alzheimer Disease, Animals, Humans, Hypoglycemic Agents, Parkinson Disease

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