Luan Hemi, Li Xuan, Zhang Wenyong, Luan Tiangang
Department of Biomedical Engineering, School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, 510006, China.
School of Medicine, Southern University of Science and Technology, Shenzhen, 518055, China.
Adv Biotechnol (Singap). 2023 Dec 12;1(4):7. doi: 10.1007/s44307-023-00007-3.
Bile acids, synthesized in the liver and modified by the gut microbiota, play vital roles in various physiological processes. The dysregulation of bile acids has been extensively documented in patients with neurodegenerative diseases. However, limited attention has been given to the protein targets associated with microbiota-derived bile acids in neurological diseases. To address this knowledge gap, we conducted comprehensive thermal proteomic analyses to elucidate and comprehend the protein targets affected by microbiota-derived bile acids. Our investigation identified sixty-five unique proteins in SH-SY5Y neuronal cells as potential targets of deoxycholic acid (DCA), a primary component of the bile acid pool originating from the gut microbiota. Notably, Nicastrin and Casein kinase 1 epsilon stood out among these proteins. We found that DCA, through its interaction with the Nicastrin subunit of γ-secretase, significantly contributed to the formation of amyloid beta, a key hallmark in the pathology of neurodegenerative diseases. In summary, our findings provide crucial insights into the intricate interplay between microbiota-derived bile acids and the pathogenesis of neurodegenerative diseases, thereby shedding light on potential therapeutic targets for neurodegenerative diseases.
胆汁酸在肝脏中合成并经肠道微生物群修饰，在各种生理过程中发挥着至关重要的作用。胆汁酸失调在神经退行性疾病患者中已有广泛记载。然而，在神经疾病中，与微生物群衍生的胆汁酸相关的蛋白质靶点却很少受到关注。为了填补这一知识空白，我们进行了全面的热蛋白质组分析，以阐明和理解受微生物群衍生胆汁酸影响的蛋白质靶点。我们的研究在SH-SY5Y神经元细胞中鉴定出65种独特蛋白质，作为脱氧胆酸（DCA）的潜在靶点，DCA是源自肠道微生物群的胆汁酸池的主要成分。值得注意的是，尼卡斯特林和酪蛋白激酶1ε在这些蛋白质中脱颖而出。我们发现，DCA通过与γ-分泌酶的尼卡斯特林亚基相互作用，显著促进了β-淀粉样蛋白的形成，β-淀粉样蛋白是神经退行性疾病病理学中的一个关键标志。总之，我们的研究结果为微生物群衍生的胆汁酸与神经退行性疾病发病机制之间的复杂相互作用提供了关键见解，从而为神经退行性疾病的潜在治疗靶点提供了线索。
