Phosphatidylinositol-3-kinase/Protein Kinase B (PI3K/AKT) and Nucleotide-Binding Oligomerization Domain-like Receptor Family Pyrin Domain Containing 3 (NLRP3) Inflammasome Modulation Underlies the Neuroprotective Effects of Vildagliptin in a Rotenone-Induced Mouse Model of Parkinson’s Disease
Abstract
studies, it was observed that vildagliptin improved motor coordination, muscle strength, and cognitive abilities. Biochemical assays show a reduction in MDA and restoration of GSH, indicating alleviation of oxidative stress. Moreover, at the molecular level, vildagliptin upregulated neuroprotective markers like PI3K, AKT, CREB, BDNF, and TH and downregulated pathological and inflammatory markers like NLRP3, IL-1β, caspase-1, gasdermin D, and α-syn. Histopathological and immunohistochemistry studies also demonstrate preservation of dopaminergic neurons. These findings collectively suggest that vildagliptin rendered neuroprotection by PI3K/AKT activation and inhibition of NLRP3-mediated neuroinflammation and apoptosis. In conclusion, we can say that vildagliptin possesses definitive neuroprotective potential as a disease-modifying therapy that warrants further clinical exploration.
Fields of Study & Subjects
Parkinson's Disease Mechanisms and Treatments
Inflammasome and immune disorders
Sphingolipid Metabolism and Signaling
Publication details
- Journal / source
- ACS Pharmacology & Translational Science
- Publisher
- American Chemical Society (ACS)
- Volume
- 9
- Issue
- 6
- Pages
- 1483–1496
- Publication date
- 1 May 2026
- Language
- EN