PDF(Pubmed)
Abstract：
Autophagy is a vital cellular process responsible for digesting various cytoplasmic organelles. This process plays a crucial role in maintaining cell survival and homeostasis, especially under conditions that cause nutrient deficiency, cellular damage, and oxidative stress. Neuroangiostrongyliasis is an infection caused by the parasitic nematode Angiostrongylus cantonensis and is considered as an emerging disease in many parts of the world. However, effective therapeutic strategies for neuroangiostrongyliasis still need to be further developed. In this study, we investigated the effects of benzaldehyde treatment on autophagy and sonic hedgehog (Shh) signaling in A. cantonensis-infected mice and its mechanisms. First, we found autophagosome generation in the central nervous system after A. cantonensis infection. Next, benzaldehyde combined with albendazole treatment reduced eosinophilic meningitis and upregulated the expression of Shh signaling- and autophagy-related molecules in A. cantonensis-infected mouse brains. In vitro experiments demonstrated that benzaldehyde could induce autophagy via the Shh signaling pathway in A. cantonensis excretory-secretory products (ESPs)-treated mouse astrocytes. Finally, benzaldehyde treatment also decreased lipid droplet accumulation and increased cholesterol production by activating the Shh pathway after ESPs treatment. In conclusion, these findings suggested that benzaldehyde treatment could alleviate brain damage by stimulating autophagy generation through the Shh signaling pathway.
摘要：
自噬是负责消化各种细胞质细胞器的重要细胞过程。这个过程在维持细胞存活和稳态中起着至关重要的作用。尤其是在导致营养缺乏的条件下，细胞损伤,和氧化应激。神经管圆线虫病是由寄生线虫引起的感染，在世界许多地方被认为是一种新兴的疾病。然而,神经管圆线虫病的有效治疗策略仍需进一步发展.在这项研究中,我们研究了苯甲醛处理对A.cantonensis感染小鼠的自噬和声刺猬（Shh）信号的影响及其机制。首先,我们发现自噬小体在感染后的中枢神经系统产生。接下来,苯甲醛与阿苯达唑联合治疗可减少嗜酸性粒细胞性脑膜炎，并上调感染广东A的小鼠大脑中Shh信号相关分子和自噬相关分子的表达。体外实验表明，苯甲醛可以通过Shh信号通路在经广东曲霉排泄分泌产物（ESPs）处理的小鼠星形胶质细胞中诱导自噬。最后,苯甲醛处理还通过在ESPs处理后激活Shh途径来减少脂滴积累和增加胆固醇产生。总之,这些发现表明，苯甲醛治疗可以通过Shh信号通路刺激自噬的产生来减轻脑损伤。
