Yang Zhengjia, Liu Tingting, Kong Xiangrui, Wei Jianshe
School of Life Sciences, Henan University, Kaifeng, P.R. China.
Mol Nutr Food Res. 2025 Jul;69(14):e70111. doi: 10.1002/mnfr.70111. Epub 2025 May 13.
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.
帕金森病（PD）是仅次于阿尔茨海默病（AD）的第二大神经退行性疾病，神经炎症是其重要病因之一。到目前为止，尚无明确证据表明药物可改善PD的发病情况，因此寻找并开发有效的PD治疗药物至关重要。脱落酸（ABA）是一种植物激素，其结构和药用功能与过氧化物酶体增殖物激活受体γ（PPAR-γ）激动剂噻唑烷二酮类药物（TZDs）相似。它在多种炎症性疾病中发挥了治疗作用，但在PD中的作用和机制尚未明确。本研究旨在深入了解ABA在1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导的PD模型中的神经保护作用及机制。在本研究中，我们观察到，除了MPTP诱导的小鼠出现明显的行为异常外，致密部黑质（SNpc）中的离子钙结合衔接分子1（IBA-1）、胶质纤维酸性蛋白（GFAP）、肿瘤坏死因子（TNF-α）、白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6）等炎症参数也显著增加。ABA治疗可恢复MPTP诱导小鼠的行为异常，并显著降低这些炎症参数。有趣的是，这些作用与兰硫氨酸合成酶C样蛋白2（LANCL2）的激活无关，而是与过氧化物酶体增殖物激活受体γ（PPAR-γ）的调节有关。腹腔注射ABA可改善MPTP诱导的PPAR-γ和过氧化物酶体增殖物激活受体共激活因子-1α（PGC-1α）表达的增加。我们的研究结果表明，腹腔注射ABA对MPTP诱导的神经退行性变具有神经保护作用，且这种作用与神经炎症的下调以及PPAR-γ和PGC-1α表达的调节有关。这些结果表明，ABA有望开发成为PD的治疗候选药物。
