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Novel GLP-1 (Glucagon-Like Peptide-1) Analogues and Insulin in the Treatment for Alzheimer’s Disease and Other Neurodegenerative Diseases

Abstract

The link between diabetes mellitus and Alzheimer’s disease (AD) has been known for the last few decades. Since insulin and insulin receptors are known to be present in the brain, the downstream signalling as well as the effect of hyperinsulinemia have been extensively studied in both AD and Parkinson’s disease. Glucagon-like peptide-1 (GLP-1) is a hormone belonging to the incretin family, and its receptors (GLP-1Rs) can be found in pancreatic cells and in vascular endothelium. Interestingly, GLP-1Rs are found in the neuronal cell body and dendrites in the central nervous system (CNS), in particular in the hypothalamus, hippocampus, cerebral cortex and olfactory bulb. Several studies have shown the importance of both insulin and GLP-1 signalling on cognitive function, and many preclinical studies have been performed to evaluate the potential protective role of GLP-1 on the brain. Here we review the underlying mechanism of insulin and GLP-1 signalling in the CNS, as well as the preclinical data for the use of GLP-1 analogues such as liraglutide, exenatide and lixisenatide in neurodegenerative diseases.

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Correspondence to Paul Edison.

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Dr. Calsolaro has nothing to disclose. Dr. Edison received funding from Novo Nordisk Pharmaceuticals and from GE Healthcare. Dr. Edison was funded by the Medical Research Council and is currently funded by the Higher Education Funding Council for England (HEFCE). He has also received grants from Alzheimer’s Research UK, Alzheimer’s Drug Discovery Foundation, the UK Alzheimer’s Society, Novo Nordisk and GE Healthcare. Dr Calsolaro received funding from Alzheimer Research, UK.

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Calsolaro, V., Edison, P. Novel GLP-1 (Glucagon-Like Peptide-1) Analogues and Insulin in the Treatment for Alzheimer’s Disease and Other Neurodegenerative Diseases. CNS Drugs 29, 1023–1039 (2015). https://doi.org/10.1007/s40263-015-0301-8

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Keywords

  • Mild Cognitive Impairment
  • MPTP
  • Liraglutide
  • Exenatide
  • Sitagliptin