Neuroprotective Effect of Abscisic Acid on MPTP-Induced Parkinson's Disease in Mice

Parkinson's disease (PD) is the second largest neurodegenerative disease after Alzheimer's disease (AD), and neuroinflammation is one of its important causes. So far, there is no clear evidence that drugs can improve the onset of PD, so it is crucial to find and develop effective drugs for PD treatment. Abscisic acid (ABA) is a phytohormone with structural and medicinal functions similar to the PPAR-γ agonist thiazolidinedione drugs (TZDs). It has played therapeutic effects in a variety of inflammatory diseases, but the role and mechanism of PD have not been defined. The present study aimed to gain insight into the neuroprotection effects and mechanism of ABA in MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-induced PD models. In this study, we observed that in addition to significant behavioral abnormalities in MPTP-induced mice, Inflammatory parameters such as ion calcium-binding adaptor molecule 1 (IBA-1), glial fibrillary acid protein (GFAP), tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) were also significantly increased in substantia nigra pars compacta (SNpc). ABA treatment restored behavioral abnormalities and significantly reduced these inflammatory parameters in MPTP-induced mice. Interestingly, these effects were not related to the activation of the lanthionine synthetase C-like protein 2 (LANCL2) but were related to the regulation of the peroxisome proliferator-activated receptor gamma (PPAR-γ). Intraperitoneal injection of ABA ameliorated the MPTP-induced increase in PPAR-γ and peroxisome proliferator-activated receptor co-activator-1α (PGC-1α) expression. Our findings suggest that intraperitoneal injection of ABA is neuroprotective against neurodegeneration induced by MPTP, and this effect is associated with the downregulation of neuroinflammation and modulation of the expression of PPAR-γ and PGC-1α. These results suggest that ABA is expected to develop as a therapeutic candidate for PD.