牛磺酸在自闭症谱系障碍中的潜在治疗作用

Alberto Rubio-Casillas, E. Redwan, V. Uversky
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引用次数: 2

摘要

当代研究发现,自闭症谱系障碍(ASD)患者表现出异常的免疫功能,细胞因子产生增加,细胞功能异常。免疫细胞化学研究发现,小胶质细胞和星形胶质细胞被显著激活,细胞因子分析显示,巨噬细胞趋化蛋白-1(MCP-1)、白细胞介素-6(IL-6)、肿瘤坏死因子α(TNF-α)和转化生长因子β-1(TGFB-1)均在神经胶质细胞中产生,构成了大脑中最主要的细胞因子。牛磺酸(2-氨基乙磺酸)是一种很有前途的治疗分子,能够提高抗氧化酶和ATP酶的活性,这可能对铝诱导的神经毒性具有保护作用。它还可以通过减少线粒体自噬和提高抗炎和促愈合M2巨噬细胞标志物的表达,如巨噬细胞甘露糖受体(MMR,CD206)和白细胞介素10(IL-10),刺激神经发生、突触发生和促炎M1巨噬细胞极化的重编程,同时降低M1炎症因子基因的表达。牛磺酸还诱导自噬,这是一种在小胶质细胞中受损的机制,与ASD的病理生理学密切相关。我们在此假设牛磺酸可以重新编程ASD患者神经系统中过度刺激的M1巨噬细胞的代谢,从而减少以自噬损伤(由于小胶质细胞过度激活)、神经元死亡为特征的神经炎症过程,并改善认知功能。因此,我们认为牛磺酸可以作为开发治疗ASD新药的重要先导。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
On the Potential Therapeutic Roles of Taurine in Autism Spectrum Disorder
Contemporary research has found that people with autism spectrum disorder (ASD) exhibit aberrant immunological function, with a shift toward increased cytokine production and unusual cell function. Microglia and astroglia were found to be significantly activated in immuno-cytochemical studies, and cytokine analysis revealed that the macrophage chemoattractant protein-1 (MCP-1), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and transforming growth factor β-1 (TGFB-1), all generated in the neuroglia, constituted the most predominant cytokines in the brain. Taurine (2-aminoethanesulfonic acid) is a promising therapeutic molecule able to increase the activity of antioxidant enzymes and ATPase, which may be protective against aluminum-induced neurotoxicity. It can also stimulate neurogenesis, synaptogenesis, and reprogramming of proinflammatory M1 macrophage polarization by decreasing mitophagy (mitochondrial autophagy) and raising the expression of the markers of the anti-inflammatory and pro-healing M2 macrophages, such as macrophage mannose receptor (MMR, CD206) and interleukin 10 (IL-10), while lowering the expression of the M1 inflammatory factor genes. Taurine also induces autophagy, which is a mechanism that is impaired in microglia cells and is critically associated with the pathophysiology of ASD. We hypothesize here that taurine could reprogram the metabolism of M1 macrophages that are overstimulated in the nervous system of people suffering from ASD, thereby decreasing the neuroinflammatory process characterized by autophagy impairment (due to excessive microglia activation), neuronal death, and improving cognitive functions. Therefore, we suggest that taurine can serve as an important lead for the development of novel drugs for ASD treatment.
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