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

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Type 2 diabetes (T2DM) and the associated de-sensitisation of insulin signalling has been identified as a risk factor for progressive neurodegenerative disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and others. Glucagon-like protein 1 (GLP-1) is a hormone that has growth-factor like and neuroprotective properties. Several clinical trials have been conducted, testing GLP-1R agonists in patients with AD, PD, or diabetes-induced memory impairments. The trials showed clear improvements in AD, PD, and in diabetic patients. Glucose-dependent insulinotropic polypeptide (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 AD and PD patients.

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Authors: Christian Hölscher