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牛磺酸通过 PI3K/Akt 信号通路保护百草枯诱导的帕金森病小鼠模型中的多巴胺能神经元。

Taurine protects dopaminergic neurons in paraquat-induced Parkinson's disease mouse model through PI3K/Akt signaling pathways.

机构信息

School of Public Health and Management, Ningxia Medical University, Yinchuan, China.

Key Laboratory of Environmental Factors and Chronic Disease Control, No.1160, Shengli Street, Xingqing District, Yinchuan, Ningxia, China.

出版信息

Amino Acids. 2022 Jan;54(1):1-11. doi: 10.1007/s00726-021-03104-6. Epub 2021 Nov 27.

Abstract

Taurine (Tau) is one of the most abundant amino acids in the brain and regulates physiological functions in the central nervous system, including anti-inflammatory effects. There is growing evidence that microglia-mediated neuro-inflammatory responses are an integral part of Parkinson's disease (PD) onset and progression. Among the many factors regulating the inflammatory response, phosphatidylinositol-3 kinase (PI3K) is susceptible to activation by a variety of cytokines and physicochemical factors, and subsequently recruits signaling proteins containing the pleckstrin homology structural domain to further regulate protein kinase B (AKT) expression involved in the regulation of the intracellular immune response and inflammatory response. Therefore, we established a PD mouse model using paraquat (PQ) intraperitoneal injection staining to explore the mechanism of Tau action on PI3K/AKT signaling pathway. Our study showed that PD mice with Tau intervention recovered motor and non-motor functions to some extent, and the number of dopaminergic (DAc) neurons in the substantia nigra and the level of dopamine (DA) secretion in the striatum were also significantly increased compared with the PQ-dyed group, and the protein content of PI3K and PDK-1 and the phosphorylation level of AKT were reduced in parallel with the reduction in the expression of microglia and related inflammatory factors. In conclusion, our results suggest that Tau may regulate microglia-mediated inflammatory responses through inhibition of the PI3K/AKT pathway in the midbrain of PD mice, thereby reducing DAc neurons damage.

摘要

牛磺酸(Tau)是脑中最丰富的氨基酸之一,调节中枢神经系统的生理功能,包括抗炎作用。越来越多的证据表明,小胶质细胞介导的神经炎症反应是帕金森病(PD)发病和进展的一个组成部分。在调节炎症反应的众多因素中,磷脂酰肌醇-3 激酶(PI3K)易受各种细胞因子和物理化学因素的激活,随后募集含有pleckstrin 同源结构域的信号蛋白,进一步调节蛋白激酶 B(AKT)的表达,参与调节细胞内免疫反应和炎症反应。因此,我们使用腹腔注射百草枯(PQ)染色建立 PD 小鼠模型,以探讨 Tau 对 PI3K/AKT 信号通路的作用机制。我们的研究表明,Tau 干预的 PD 小鼠在一定程度上恢复了运动和非运动功能,黑质纹状体中的多巴胺能(DAc)神经元数量和纹状体中多巴胺(DA)分泌水平也明显高于 PQ 染色组,同时,PI3K 和 PDK-1 的蛋白含量以及 AKT 的磷酸化水平与小胶质细胞和相关炎症因子表达的减少呈平行下降趋势。总之,我们的结果表明,Tau 可能通过抑制 PD 小鼠中脑的 PI3K/AKT 通路来调节小胶质细胞介导的炎症反应,从而减轻 DAc 神经元损伤。

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