Abstract

The incretin hormone GLP-1 has many effects in the body. It is best known for the 'incretin effect', facilitating insulin release from the pancreas in hyperglycaemic conditions. Building on this, GLP-1 mimetics have been developed as a treatment for type 2 diabetes. In the course of monitoring of patients, it has become apparent that GLP-1 mimetics have a range of other physiological effects in the body. In preclinical trials, a substantial body of evidence has been built that these mimetics have neuroprotective and anti-inflammatory effects. GLP-1 also has very similar growth-factor like properties as insulin, which presumable is the underlying basis of the neuroprotective effects. In preclinical studies of Alzheimer's disease (AD), Parkinson's disease (PD), stroke and other neurodegenerative disorders, it has been shown that most GLP-1 mimetics crosss the blood brain barrier and show impressive neuroprotective effects in numerous studies. In animal models of Alzheimer's disease, GLP-1 mimetics such as exendin-4, liraglutide, and lixisenatide have shown protective effects in the CNS by reducing beta-amyloid plaques, preventing loss of synapses and memory impairments, and reducing oxidative stress and the chronic inflammation response in the brain. In animal models of PD, exendin-4 showed protection of dopaminergic neurons in the substantia nigra and prevention of dopamine loss in the basal ganglia while preserving motor control. These encouraging findings have spawned several clinical trials, some of which have shown first encouraging results. Therefore, GLP-1 mimetics show great promise as a novel treatment for neurodegenerative conditions.