GLP-1 agonist and neuroprotection in Stroke and Parkinson's disease: A systematic review.
This systematic review (PRISMA-guided) examined whether GLP-1 receptor agonists (GLP-1 RAs) exert neuroprotective effects in preclinical models of stroke and Parkinson's disease (PD). Researchers searched four major databases (Cochrane CENTRAL, PubMed, Web of Science, Scopus), identifying 1,643 records and ultimately including 13 experimental animal studies published between 2013 and 2026. For stroke, studies primarily used middle cerebral artery occlusion (MCAO) models; the review found that agents such as liraglutide and linagliptin were associated with notable reductions in infarct volume and improved neurological deficit scores in treated animals. For PD models, the included studies reported improvements in motor function, preservation of dopaminergic neurons, and reduced α-synuclein aggregation. Across both disease models, GLP-1 RAs appeared to modulate neuroinflammatory markers (TNF-α, IL-1β, IL-6), oxidative stress indicators (ROS, 4-HNE), and apoptotic pathways (increased Bcl-2, decreased Bax). Risk of bias assessment using the SYRCLE tool rated overall quality as moderate, with four studies flagged as high risk due to small sample sizes and inadequate reporting of randomization and blinding procedures. The authors concluded that while preclinical evidence appears promising, standardized studies and clinical trials are needed before translational conclusions can be drawn.
Why this grade: Although this is a systematic review, all 13 included studies are experimental animal studies with no human clinical data, limiting evidence applicability to humans.
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.
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