title: The role of GLP-1 in neuronal activity and neurodegeneration.
abstract: Type 2 diabetes has been identified as a risk factor for Alzheimer's disease (AD). The underlying mechanism behind this unexpected link is most likely linked to the observed desensitization of insulin receptors in the brain. Insulin acts as a growth factor in the brain and supports neuronal repair, dendritic sprouting, and differentiation. Several drugs have been developed to treat type 2 diabetes which re-synthesize insulin receptors and may be of use to prevent neurodegenerative developments in AD. The incretin glucagon-like peptide-1 (GLP-1) is a hormone that facilitates insulin release under high blood sugar conditions. Interestingly, GLP-1 also has very similar growth factor like properties as insulin, and has been shown to protect neurons from toxic effects. In preclinical studies, GLP-1 and longer lasting analogues reduce apoptosis, protect neurons from oxidative stress, induce neurite outgrowth, protect synaptic plasticity and memory formation from the detrimental effects of β-amyloid, and reduce plaque formation and the inflammation response in the brains of mouse models of AD. An advantage of GLP-1 is that it does not affect blood sugar levels in nondiabetic people. Furthermore, recent research has shown that some GLP-1 analogues can cross the blood-brain barrier, including two that are on the market as a treatment for type 2 diabetes. Therefore, GLP-1 analogues show great promise as a novel treatment for AD or other neurodegenerative conditions.
authors.affiliation: School of Biomedical Sciences, University of Ulster, Coleraine, Northern Ireland, United Kingdom.
authors.forename: Christian
authors.initials: C
authors.lastname: Hölscher
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives / Q000502:physiology*; D006801:Humans; D009410:Nerve Degeneration / Q000503:physiopathology*; D011972:Receptor, Insulin / Q000502:physiology*
chemical_list: D052216:Glucagon-Like Peptide 1; D011972:Receptor, Insulin