Neuroprotection Against Parkinson's Disease Through the Activation of Akt/GSK3β Signaling Pathway by Tovophyllin A
Neuroprotection Against Parkinson's Disease Through the Activation of Akt/GSK3β Signaling Pathway by Tovophyllin A
复制标题
DOI：
10.3389/fnins.2020.00723
复制
发表时间：
2020-07-09
影响因子：
4.3
通讯作者：
Wang, Xuemin
中科院分区：
文献类型：
--
作者：
Huang, Yanjun;Sun, Lirong;Wang, Xuemin
帕金森病（Parkinson's disease，PD）是一种常见的神经退行性疾病，其主要特征是黑质多巴胺能神经元缺乏。虽然目前的治疗有助于缓解临床症状，但预防神经元损失的有效疗法仍然很少。托伏叶素A（Tovophyllin A，TA）是从山竹（Garcinia mangostanaL.）(GM)最近已经报道在神经变性疾病的治疗中发挥有益的作用。本研究探讨TA对PD模型多巴胺能神经元是否具有保护作用。我们发现，TA显着减少1-甲基-4-苯基吡啶（MPP+）或百草枯（PQ）处理的原代皮层神经元在体外PD模型中的细胞凋亡。在1-甲基-4-苯基-1，2，3，5-四氢吡啶（MPTP）诱导的急性PD动物模型中，TA也能减轻由此引起的行为障碍和多巴胺能神经元丢失。在收集的脑组织中，TA增加Akt和GSK-3 β的磷酸化，这可能与TA介导的多巴胺能神经元保护作用有关。总之，我们的研究结果表明，TA是一个强大的细胞保护剂的多巴胺能神经元在MPTP诱导的PD模型，表明TA作为一个可能的治疗PD的候选人。
Parkinson's disease (PD) is one of the most prevalent and life-threatening neurodegenerative disease and mainly characterized by lack of sufficient dopaminergic neurons in the substantia nigra pars compacta (SNc). Although current treatments help to alleviate clinical symptoms, effective therapies preventing neuronal loss remain scarce. Tovophyllin A (TA), one of the xanthones extracted fromGarcinia mangostanaL. (GM), has recently been reported to play a beneficial role in the therapy of neurodegenerative diseases. In our research, we explored whether TA has protective effects on dopaminergic neurons in PD models. We found that TA significantly reduced apoptotic cell death in primary cortical neurons treated with 1-methyl-4-phenyl pyridinium (MPP+) or paraquat (PQ) in thein vitroPD model. In anin vivoacute PD model induced by 1-methyl4-phenyl-1,2,3,5-tetrahydropyridine (MPTP) treatment, TA also attenuated the resulting behavioral dysfunctions and dopaminergic neuron loss. In the collected brain tissues, TA increased the phosphorylation of Akt and GSK-3 beta, which may be related to TA-mediated dopaminergic neuronal protective effects. In summary, our results illustrated that TA is a powerful cytoprotective agent for dopaminergic neurons in the MPTP-induced PD model, suggesting TA as a possible therapeutic candidate for PD.