Protective properties of GLP‐1 and associated peptide hormones in neurodegenerative disorders

Abstract

Type 2 diabetes mellitus and the associated desensitisation of insulin signalling has been identified as a risk factor for progressive neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and others. Glucagon-like peptide 1 (GLP-1) is a hormone that has growth factor-like and neuroprotective properties. Several clinical trials have been conducted, testing GLP-1 receptor agonists in patients with Alzheimer's disease, Parkinson's disease or diabetes-induced memory impairments. The trials showed clear improvements in Alzheimer's disease, Parkinson's disease and diabetic patients. Glucose-dependent insulinotropic polypeptide/gastric inhibitory peptide (GIP) is the 'sister' incretin hormone of GLP-1. GIP analogues have shown neuroprotective effects in animal models of disease and can improve on the effects of GLP-1. Novel dual GLP-1/GIP receptor agonists have been developed that can enter the brain at an enhanced rate. The improved neuroprotective effects of these drugs suggest that they are superior to single GLP-1 receptor agonists and could provide disease-modifying care for Alzheimer's disease and Parkinson's disease patients. LINKED ARTICLES: This article is part of a themed issue on GLP1 receptor ligands (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.4/issuetoc.