The DOI matches its Crossref record; 306 of the 306 references it cites were found in a registry or an index.
Glucagon-like peptide-1 (GLP-1) receptor agonists and neuroinflammation: Implications for neurodegenerative disease treatment
Open accessAbstract
Chronic, excessive neuroinflammation is a key feature of neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). However, neuroinflammatory pathways have yet to be effectively targeted in clinical treatments for such diseases. Interestingly, increased inflammation and neurodegenerative disease risk have been associated with type 2 diabetes mellitus (T2DM) and insulin resistance (IR), suggesting that treatments that mitigate T2DM pathology may be successful in treating neuroinflammatory and neurodegenerative pathology as well. Glucagon-like peptide-1 (GLP-1) is an incretin hormone that promotes healthy insulin signaling, regulates blood sugar levels, and suppresses appetite. Consequently, numerous GLP-1 receptor (GLP-1R) stimulating drugs have been developed and approved by the US Food and Drug Administration (FDA) and related global regulatory authorities for the treatment of T2DM. Furthermore, GLP-1R stimulating drugs have been associated with anti-inflammatory, neurotrophic, and neuroprotective properties in neurodegenerative disorder preclinical models, and hence hold promise for repurposing as a treatment for neurodegenerative diseases. In this review, we discuss incretin signaling, neuroinflammatory pathways, and the intersections between neuroinflammation, brain IR, and neurodegenerative diseases, with a focus on AD and PD. We additionally overview current FDA-approved incretin receptor stimulating drugs and agents in development, including unimolecular single, dual, and triple receptor agonists, and highlight those in clinical trials for neurodegenerative disease treatment. We propose that repurposing already-approved GLP-1R agonists for the treatment of neurodegenerative diseases may be a safe, efficacious, and cost-effective strategy for ameliorating AD and PD pathology by quelling neuroinflammation.
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“GLP-1R agonists, approved for the treatment of type 2 diabetes and obesity, have demonstrated promising neuroprotective effects in neurodegenerative diseases owing to their ability to suppress neuroinflammation.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [598]
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“Substantial preclinical evidence supports the neuroprotective effects of GLP-1R agonists on cognition in AD, which is attributed to the ability to reduce Aβ pathology, tau phosphorylation, glial activation, and neuroinflammation.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [598]
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“However, GLP-1 RAs enhance motor performance and dopamine signalling and inhibit the aggregation of α-syn in PD models, possibly by regulating the Akt pathway.423,427”
From Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances (2025) · cites this paper as [427]
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Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases
Loh, J. S., Mak, W. Q., Tan, L. K. S., Ng, C. X., Chan, H. H., Yeow, S. H., Foo, J. B., Ong, Y. S., How, C. W., & Khaw, K. Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01743-1 · Cited by 1,193
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Metadata
- Authors
- Kopp, K. O., Glotfelty, E. J., Li, Y., & Greig, N. H.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Kopp, Katherine O.
- Greig, Nigel H.
- Venue
- Pharmacological Research
- Publisher
- Elsevier BV
- Published
- 2022-12
- Volume
- 186
- Pages
- 106550
- ISSN
- 1043-6618 (ISSN-L)
- PMC
- PMC9712272
- OpenAlex
- W4308952350
- Cited by
- 298
- References
- 306
- Citations by year
- 2026: 92 · 2025: 122 · 2024: 63 · 2023: 21
- FWCI
- 5.31
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Pharmacological Research (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (AG000333)
- National Institutes of Health
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- GLP-1 receptor agonists, neuroinflammation, neurodegenerative diseases, Alzheimer's disease, Parkinson's disease, type 2 diabetes, insulin resistance, incretin signaling, drug repurposing, neuroprotection, anti-inflammatory activity
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Neuroinflammatory Diseases, Glucagon-Like Peptide-1 Receptor Agonists, Alzheimer Disease, Diabetes Mellitus, Type 2, Humans, Parkinson Disease, Neurodegenerative Diseases, Glucagon-Like Peptide 1, Incretins
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