The glucagon-like peptide 1 (GLP) receptor as a therapeutic target in Parkinson's disease: mechanisms of action
Open accessAbstract
Growing evidence suggests that agonists of the glucagon-like peptide 1 (GLP-1) receptor provide neuroprotection across a range of experimental models of Parkinson's disease (PD) and, recently, a small proof-of-concept, open-label human trial of exenatide in the treatment moderate severity PD appeared to show persistent improvements in motor and cognitive function. The underlying mechanisms of action remain unclear, but as evidence for the potential use of GLP-1 agonists in treating several neurodegenerative disease mounts, and with several clinical trials of GLP-1 analogues in PD and Alzheimer's disease (AD) currently underway, here we review the molecular mechanisms underlying the neuroprotective effects of GLP-1 analogues in the laboratory and their potential therapeutic utility with particular relevance to PD and PD dementia (PDD).
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GLP-1 is an endogenous hormone secreted by ileal endocrine cells, which promotes insulin secretion in a hyperglycemic environment.
“Glucagon-like peptide-1 (GLP-1) is an endogenous hormone secreted by ileal endocrine cells, which promotes insulin secretion in a hyperglycemic environment (Athauda and Foltynie 2016).”
From Therapeutic effect of GLP-1 engineered strain on mice model of Alzheimer’s disease and Parkinson’s disease (2020) · cites this paper as Athauda and Foltynie 2016
GLP-1 is an enterogenous hormone that promotes insulin secretion and reduces glucagon secretion to reduce blood glucose in a glucose concentration-dependent manner.
“GLP-1 is an enterogenous hormone that promotes insulin secretion and reduces glucagon secretion to reduce blood glucose in a glucose concentration-dependent manner (Athauda and Foltynie 2016).”
From Therapeutic effect of GLP-1 engineered strain on mice model of Alzheimer’s disease and Parkinson’s disease (2020) · cites this paper as Athauda and Foltynie 2016
GLP-1 is easily degraded, requiring continuous intravenous drip or continuous subcutaneous injection to produce therapeutic effects, which limits its clinical usage.
“However, as GLP-1 is easily degraded, continuous intravenous drip or continuous subcutaneous injection is required to produce therapeutic effects, which limits its clinical usage.”
From Therapeutic effect of GLP-1 engineered strain on mice model of Alzheimer’s disease and Parkinson’s disease (2020) · cites this paper as Athauda and Foltynie 2016
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- Authors
- Athauda, D., & Foltynie, T.
- Affiliations
- National Hospital for Neurology and Neurosurgery (GB)
- Corresponding author
- Athauda, Dilan
- Venue
- Drug Discovery Today
- Publisher
- Elsevier BV
- Published
- 2016-05
- Volume
- 21
- Issue
- 5
- Pages
- 802-818
- ISSN
- 1359-6446 (ISSN-L)
- OpenAlex
- W2270971263
- Cited by
- 383
- References
- 258
- Citations by year
- 2026: 38 · 2025: 51 · 2024: 53 · 2023: 31 · 2022: 46 · 2021: 34 · 2020: 42 · 2019: 32 · 2018: 29 · 2017: 19 · 2016: 8
- FWCI
- 4.07
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Drug Discovery Today (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Michael J. Fox Foundation, Brain Research Trust, Cure Parkinson's Trust, Parkinson's UK
- European Commission (FP7)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- GLP-1 receptor, GLP-1 receptor agonists, Parkinson's disease, neuroprotection, exenatide, Parkinson's disease dementia, Alzheimer's disease, mechanism of action, therapeutic target
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Alzheimer Disease, Animals, Humans, Insulin Resistance, Learning, Mitochondria, Parkinson Disease, Signal Transduction, Proto-Oncogene Proteins c-akt, Glucagon-Like Peptide 1, Neurogenesis
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