Neuroprotective properties of incretin mimetics in brain ischemia and neurodegenerative diseases

Abstract

Type 2 diabetes mellitus (DMT2) is a disease significantly increasing the risk of neurodegenerative disorders and stroke. The keen interest in anti-diabetic medications, which can reduce the risk of cardiovascular and neurodegenerative disorders, is caused by the substantial rise in the number of patients with DMT2 as a result of population aging. According to the clinical trial data, incretin mimetics significantly reduce the glycosylated hemoglobin level, while moderately reducing blood pressure and adipose tissue mass in DMT2patients. When added to the conventional hypoglycemic therapy, analogues of glucagon-like peptide-1 (GLP-1) significantly decrease the risk of cardiovascular complications in DMT2 patients. The positive effect of these medications in patients with neurodegenerative diseases, both the independent and T2DM-associated ones, has been observed. Today, there are ongoing clinical trials of the effect of GLP-1 analogues in patients with Parkinson's and Alzheimer's disease. The available data show that incretin mimetics exhibit neuroprotective properties due to GLP-1 receptors on neurons, microglial and endothelial cells. These receptors were found to be able to trigger the major intracellular signaling pathways that maintain cellular function and inhibit apoptosis under pathological conditions. In this review, we summarize the results of studies focused on neuroprotective properties of drugs with the incretin-mimetic mechanism of action. The findings on their effect on a number of pathological processes in patients with neurodegenerative diseases and cerebrovascular disturbance are reported. The ability of incretin mimetics to reduce microglial activation, secretion of proinflammatory cytokines and pathological protein aggregation, as well as inhibit neuronal apoptosis, improve mitochondrial functional state, enhance expression of trophic factors and stimulate neurogenesis, is demonstrated.