Incretin Analogues that have been Developed to Treat Type 2 Diabetes Hold Promise as a Novel Treatment Strategy for Alzheimers Disease
Abstract
Analogues of the incretins Glucagon-like peptide 1 (GLP-1) and Glucose-dependent insulinotropic peptide (GIP) have been developed to treat type 2 diabetes mellitus. They are protease resistant and have a longer biological half life than the native peptides. Some of these novel analogues can cross the blood-brain barrier, have neuroprotective effects, activate neuronal stem cells in the brain, and can improve cognition. The receptors for GIP and GLP-1 are expressed in neurons, and both GIP and GLP-1 are expressed and released as transmitters by neurons. GIP analogues such as DAla(2)GIP and GLP-1 analogues such as liraglutide enhance synaptic plasticity in the brain and also reverse the betaamyloid induced impairment of synaptic plasticity. In mouse models of Alzheimer's disease, GLP-1 analogues Val(8)GLP-1 and liraglutide prevent memory impairment and the block of synaptic plasticity in the brain. Since two GLP- 1 analogues exendin-4 (Exenatide, Byetta) and liraglutide (Victoza) are already on the market as treatments for Type 2 diabetes, and others are in late stage clinical trials, these drugs show promise as treatments for neurodegenerative diseases such as Alzheimer's disease. Currently, there are three patents covering native GLP-1 and different GLP-1 analogues and one patent for the use of GIP and different GIP analogues for the treatment of neurodegenerative diseases.
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GLP-1 is known to be produced in the brain and has many functions including neuroprotection.
“GLP-1 is known to be produced in the brain [79] and has many functions including neuroprotection [80–82].”
From Anti-Inflammatory Effects of GLP-1-Based Therapies beyond Glucose Control (2016) · cites this paper as [81]
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- Authors
- Holscher, C.
- Venue
- Recent Patents on CNS Drug Discovery
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2010-06-01
- Volume
- 5
- Issue
- 2
- Pages
- 109-117
- ISSN
- 1574-8898 (ISSN-L)
- OpenAlex
- W2041102868
- Cited by
- 102
- References
- 7
- Citations by year
- 2025: 2 · 2024: 3 · 2023: 3 · 2022: 7 · 2021: 6 · 2020: 6 · 2019: 5 · 2018: 4 · 2017: 4 · 2016: 7 · 2015: 10 · 2014: 8 · 2013: 11 · 2012: 14
- FWCI
- 7.96
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Recent Patents on CNS Drug Discovery (publishedVersion)
- PubMed (publishedVersion)
- Lancaster EPrints (Lancaster University) (submittedVersion)
- 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
- incretin analogues, Alzheimer's disease, type 2 diabetes, GLP-1 receptor, GIP receptor, liraglutide, exenatide, synaptic plasticity, amyloid-beta, neuroprotection, neuronal stem cells, memory impairment, blood-brain barrier, patents
- MeSH terms
- Alzheimer Disease, Amino Acid Sequence, Animals, Blood-Brain Barrier, Diabetes Mellitus, Type 2, Gastric Inhibitory Polypeptide, Humans, Models, Neurological, Molecular Sequence Data, Patents as Topic, Neuroprotective Agents, Glucagon-Like Peptide 1, Incretins
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