A New Treatment Strategy for Parkinson's Disease through the Gut–Brain Axis: The Glucagon-Like Peptide-1 Receptor Pathway
Open accessAbstract
Molecular communications in the gut–brain axis, between the central nervous system and the gastrointestinal tract, are critical for maintaining healthy brain function, particularly in aging. Epidemiological analyses indicate type 2 diabetes mellitus (T2DM) is a risk factor for neurodegenerative disorders including Alzheimer's disease (AD) and Parkinson's diseases (PD) for which aging shows a major correlative association. Common pathophysiological features exist between T2DM, AD, and PD, including oxidative stress, inflammation, insulin resistance, abnormal protein processing, and cognitive decline, and suggest that effective drugs for T2DM that positively impact the gut–brain axis could provide an effective treatment option for neurodegenerative diseases. Glucagon-like peptide-1 (GLP-1)-based antidiabetic drugs have drawn particular attention as an effectual new strategy to not only regulate blood glucose but also decrease body weight by reducing appetite, which implies that GLP-1 could affect the gut–brain axis in normal and pathological conditions. The neurotrophic and neuroprotective effects of GLP-1 receptor (R) stimulation have been characterized in numerous in vitro and in vivo preclinical studies using GLP-1R agonists and dipeptidyl peptidase-4 inhibitors. Recently, the first open label clinical study of exenatide, a long-acting GLP-1 agonist, in the treatment of PD showed long-lasting improvements in motor and cognitive function. Several double-blind clinical trials of GLP-1R agonists including exenatide in PD and other neurodegenerative diseases are already underway or are about to be initiated. Herein, we review the physiological role of the GLP-1R pathway in the gut–brain axis and the therapeutic strategy of GLP-1R stimulation for the treatment of neurodegenerative diseases focused on PD, for which age is the major risk factor.
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GLP-1 has a neuroprotective effect in the CNS, affecting proliferation and apoptosis of neural cells, improving learning, memory and motor dysfunction, reducing Aβ plaque deposition, decreasing loss of dopaminergic neurons, and promoting nerve regeneration.
“There are studies indicate that GLP-1 has a neuroprotective effect in the central nervous system (CNS), which affects the proliferation and apoptosis of neural cells, improves learning, memory and motor dysfunction, reduces the deposition of Aβ plaques in the brain, decreases the loss of dopaminergic neurons and promotes nerve regeneration (Kim et al. 2017).”
From Therapeutic effect of GLP-1 engineered strain on mice model of Alzheimer’s disease and Parkinson’s disease (2020) · cites this paper as Kim et al. 2017
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- Authors
- Kim, D. S., Choi, H.-I., Wang, Y., Luo, Y., Hoffer, B. J., & Greig, N. H.
- Affiliations
- National Institutes of Health (US)
- Peptron Inc., Yuseong-gu, Daejeon, Republic of Korea
- National Health Research Institutes (TW)
- Case Western Reserve University (US)
- Corresponding author
- Kim, Dong Seok
- Greig, Nigel H.
- Venue
- Cell Transplantation
- Publisher
- SAGE Publications
- Published
- 2017-09
- Volume
- 26
- Issue
- 9
- Pages
- 1560-1571
- ISSN
- 0963-6897 (ISSN-L)
- 1555-3892
- PMC
- PMC5680957
- OpenAlex
- W2609107212
- Cited by
- 136
- References
- 113
- Citations by year
- 2025: 12 · 2024: 15 · 2023: 15 · 2022: 29 · 2021: 20 · 2020: 19 · 2019: 14 · 2018: 10 · 2017: 2
- FWCI
- 1.64
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Cell Transplantation (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS094152)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- Parkinson's disease, gut-brain axis, GLP-1 receptor agonists, exenatide, type 2 diabetes, neurodegenerative diseases, neuroprotection, aging, DPP-4 inhibitors, oxidative stress, inflammation, insulin resistance, motor and cognitive function
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Exenatide, Animals, Blood Glucose, Humans, Hypoglycemic Agents, Parkinson Disease, Peptides, Venoms, Neuroprotective Agents, Glucagon-Like Peptide 1
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