Parkinson’s disease (PD) is one of the most widespread neurodegenerative diseases. However, the currently available treatments could only relieve symptoms. Novel therapeutic targets are urgently needed. Several previous studies mentioned that protein tyrosine phosphatase 1B (PTP1B) acted as a negative regulator of the insulin signal pathway and played a significant role in the inflammation process. However, few studies have investigated the role of PTP1B in the central nervous system. Our study showed that suramin, an inhibitor of PTP1B, could improve neuronal damage. It could significantly attenuate the interferon-gamma-induced upregulation of proinflammatory cytokines, including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). It enhanced M2 type microglia markers, such as arginase-1 and Ym-1 in BV2 murine microglial cells. PTP1B inhibition also reversed 6-hydroxydopamine- (6-OHDA-) induced downregulation of phospho-cAMP response element-binding protein (p-CREB) and brain-derived neurotrophic factor (BDNF) in SH-SY5Y cells. Besides, we knocked down and overexpressed PTP1B in the SH-SY5Y cells to confirm its role in neuroprotection. We also verified the effect of suramin in the zebrafish PD model. Treatment with suramin could significantly reverse 6-OHDA-induced locomotor deficits and improved tyrosine hydroxylase (TH) via attenuating endoplasmic reticulum (ER) stress biomarkers. These results support that PTP1B could potentially regulate PD via antineuroinflammation and antiapoptotic pathways.

中文翻译：

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酪氨酸蛋白磷酸酶1B在帕金森氏病中通过体内和体外抗神经炎和神经保护作用的治疗作用

帕金森氏病（PD）是最广泛的神经退行性疾病之一。但是，当前可用的治疗方法只能缓解症状。迫切需要新的治疗靶标。先前的一些研究提到蛋白质酪氨酸磷酸酶1B（PTP1B）充当胰岛素信号通路的负调节剂，并在炎症过程中起重要作用。但是，很少有研究调查PTP1B在中枢神经系统中的作用。我们的研究表明，苏拉明（一种PTP1B抑制剂）可以改善神经元损伤。它可以显着减弱干扰素-γ诱导的促炎细胞因子的上调，包括诱导型一氧化氮合酶（iNOS），环氧合酶-2（COX-2）和核因子kappa-轻链增强子（NF-κB）κB）。它增强了BV2鼠小胶质细胞中的M2型小胶质细胞标志物，如精氨酸酶1和Ym-1。PTP1B抑制也逆转了SH-SY5Y细胞中6-羟基多巴胺（6-OHDA-）诱导的磷酸化cAMP反应元件结合蛋白（p-CREB）和脑源性神经营养因子（BDNF）的下调。此外，我们敲低了SH-SY5Y细胞中PTP1B的表达，以证实其在神经保护中的作用。我们还验证了苏拉明在斑马鱼PD模型中的作用。苏拉明治疗可通过减弱内质网（ER）应激生物标记显着逆转6-OHDA引起的运动功能障碍并改善酪氨酸羟化酶（TH）。这些结果支持PTP1B可能通过反神经炎和抗凋亡途径调节PD。