接触会通过激活大脑中的cGAS-STING通路来诱导自 - 淋巴体通路功能障碍 - 中介性陶病症

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Xin Zhang¹, Jingjing Liu¹, Shiyin Zhong¹

¹Department of Toxicology, School of Public Health, Lanzhou University, Gansu 730000, China.

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概括

暴露于会通过cGAS-STING通路破坏自-溶解体通路引起神经退行,从而导致Tau聚合和潜在的神经毒性.

科学领域:

神经科学是一个神经科学.
毒理学毒理学毒理学
细胞生物学细胞生物学

背景情况:

(Mn) 暴露与神经退行性疾病和Tau病理有关.
人们对Mn诱导神经毒性的确切机制尚不完全了解.
自 - lysosomal 途径的功能障碍与神经退行性过程有关.

研究的目的:

阐明Mn暴露诱导自 - lysosomal通路功能障碍和陶病的机制.
研究cGAS-STING通路在Mn诱导的神经毒性中的作用.
探索缓解Mn诱导的神经退行症的潜在治疗点.

主要方法:

使用BV2微质细胞的体外研究和使用暴露于的小鼠的体内研究.
评估病,cGAS-STING通路的激活,I型干扰素的产生,以及自-溶酶体通路的功能.
使用了cGAS-knockout和STING-knockout模型,并使用了自抑制剂3-甲基氨酸 (3-MA).

主要成果:

暴露激活了cGAS-STING通路,诱导了I型干扰素,并在微质细胞和小鼠中损害了自-溶酶体通路的降解.
通过cGAS-STING通路的失活 (通过淘汰赛或3-MA) 恢复了自-溶酶体功能,并减轻了Mn诱导的陶病症.
在恢复自-溶酶体通路功能后,观察到Tau聚合的清除.

结论:

暴露于Mn会通过激活cGAS-STING通路来诱导病,从而导致自-溶酶体通路功能受损.
cGAS-STING通路是Mn诱导的神经毒性和Tau聚合的关键调解者.
准cGAS-STING通路为Mn诱导的神经退行性疾病提供了潜在的治疗策略.

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