| Incretin analogues that have been developed to treat type 2 diabetes hold promise as a novel treatment strategy for Alzheimer's disease. | |
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MedLine Citation:
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PMID: 20337586 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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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Authors:
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Christian Holscher |
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Publication Detail:
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Type: Journal Article; Review |
Journal Detail:
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Title: Recent patents on CNS drug discovery Volume: 5 ISSN: 2212-3954 ISO Abbreviation: Recent Pat CNS Drug Discov Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-06-03 Completed Date: 2010-09-07 Revised Date: 2011-11-10 |
Medline Journal Info:
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Nlm Unique ID: 101265656 Medline TA: Recent Pat CNS Drug Discov Country: United Arab Emirates |
Other Details:
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Languages: eng Pagination: 109-17 Citation Subset: IM |
Affiliation:
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School of Biomedical Sciences, Ulster University, Cromore road, Coleraine BT52 1SA, UK. c.holscher@ulster.ac.uk |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Alzheimer Disease
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drug therapy* Amino Acid Sequence Animals Blood-Brain Barrier / metabolism Diabetes Mellitus, Type 2 / drug therapy* Gastric Inhibitory Polypeptide / analogs & derivatives, pharmacology, therapeutic use* Glucagon-Like Peptide 1 / analogs & derivatives, pharmacology, therapeutic use* Humans Incretins / therapeutic use* Models, Neurological Molecular Sequence Data Neuroprotective Agents / pharmacology, therapeutic use* Patents as Topic |
| Chemical | |
Reg. No./Substance:
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0/Incretins; 0/Neuroprotective Agents; 59392-49-3/Gastric Inhibitory Polypeptide; 89750-14-1/Glucagon-Like Peptide 1 |
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