Incretin Analogues that have been Developed to Treat Type 2 Diabetes Hold Promise as a Novel Treatment Strategy for Alzheimers Disease

Author(s): Christian Holscher.

Journal Name: Recent Patents on CNS Drug Discovery (Discontinued)

Volume 5 , Issue 2 , 2010

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 Alzheimers 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 Alzheimers 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.

Keywords: Alzheimer's disease, incretins, glucagon-like peptide 1, gastric inhibitory polypeptide, glucose-dependent insulinotropic peptide, GIP, GLP-1, neurodegeneration

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Article Details

VOLUME: 5
ISSUE: 2
Year: 2010
Page: [109 - 117]
Pages: 9
DOI: 10.2174/157488910791213130
Price: $58

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