Neuroprotective properties of incretin mimetics in brain ischemia and neurodegenerative diseases

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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.


Ivan N. Tyurenkov

fibfuv@mail.ru
ORCID iD: 0000-0001-7574-3923
SPIN-code: 6195-6378
Volgograd State Medical University
Russian Federation, 3, Pugachevskaya street, Volgograd, 400001

MD, PhD, Professor

Dmitry A. Bakulin

Author for correspondence.
mbfdoc@gmail.com
ORCID iD: 0000-0003-4694-3066
SPIN-code: 3339-7228
Volgograd State Medical University
Russian Federation, 3, Pugachevskaya street, Volgograd, 400001 

MD

Denis V. Kurkin

strannik986@mail.ru
ORCID iD: 0000-0002-1116-3425
SPIN-code: 8771-1461
Volgograd State Medical University
Russian Federation, 3, Pugachevskaya street, Volgograd, 400001

PhD

Elena V. Volotova

a-zlato@mail.ru
ORCID iD: 0000-0003-3916-7249
SPIN-code: 1483-0915
Volgograd State Medical University
Russian Federation, 3, Pugachevskaya street, Volgograd, 400001

MD, PhD

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