GLP-1 agonist and neuroprotection in Stroke and Parkinson's disease: A systematic review

Glucagon-like peptide-1 receptor agonists have been shown to have neuroprotective effects in metabolic diseases, but their application in neurodegenerative diseases (stroke and Parkinson's disease) has not been adequately studied.

To assess the neuroprotective effects of GLP-1 receptor agonists in experimental stroke and Parkinson's disease models, in terms of mechanisms, properties of intervention, and major neurological outcomes.

A systematic review was performed according to PRISMA. Four databases Cochrane CENTRAL, PubMed, Web of Science and Scopus were searched and 1643 records identified and 13 experimental animal studies were included. The SYRCLE tool was used to extract data and assess the risk of bias.

13 experimental studies published in 2013-2026 were included, which involved models of stroke and Parkinson disease. The MCAO models were the main models used in stroke studies, with a significant decrease in infarct volume, such as 15.4 % ± 1.3 % (liraglutide) and 40 % reduction with linagliptin. The score in neurological deficit was also found to improve (1.1 ± 0.14; P < 0.05) and the size of the infarct in treated groups had also reduced (36.5 % to 8.2 %; P = 0.001). The research on Parkinson disease showed that there was a notable improvement in motor functions (P < 0.001), preservation of dopaminergic neurons, and a decrease in the aggregation of α-synuclein. GLP-1 agonists decreased neuroinflammatory (TNF-α, IL-1b, IL-6), oxidative (ROS, 4-HNE), and apoptotic (increased Bcl-2, decreased Bax) markers. The treatment was between 24 h and 20 weeks, and the doses also differed among the agents. The overall quality of risk of bias assessment was moderate, with four studies having a high risk because of small sample size and inadequate reporting on the randomization and blinding.

GLP-1 receptor agonists have powerful neuroprotective activity in preclinical models of stroke and Parkinson disease, which is multi-targeted. To ensure translational potential and to maximize therapeutic strategies, standardized studies and clinical trials are needed.