Department of Life Science, Bergman Campus, Ben-Gurion University of the Negev, 8441901, Beer-Sheva, Israel.
Department of Chemical Research Support, The Weizmann Institute of Science, 7610001, Rehovot, Israel.
Sci Rep. 2024 Aug 6;14(1):18247. doi: 10.1038/s41598-024-68645-8.
In the search for the origin of Amyotrophic Lateral Sclerosis disease (ALS), we hypothesized earlier (Monselise, 2019) that D-amino acids produced by stressed microbiome may serve as inducers of the disease development. Many examples of D-amino acid accumulation under various stress conditions were demonstrated in prokaryotic and eukaryotic cells. In this work, wild-type Escherichia coli, members of the digestive system, were subjected to carbon and nitrogen starvation stress. Using NMR and LC-MS techniques, we found for the first time that D-glutamate accumulated in the stressed bacteria but not in control cells. These results together with the existing knowledge, allow us to suggest a new insight into the pathway of ALS development: D-glutamate, produced by the stressed microbiome, induces neurobiochemical miscommunication setting on C1q of the complement system. Proving this insight may have great importance in preventive medicine of such MND modern-age diseases as ALS, Alzheimer, and Parkinson.
在寻找肌萎缩侧索硬化症（ALS）疾病的起源时，我们之前假设（Monselise，2019），压力微生物组产生的 D-氨基酸可能作为疾病发展的诱导剂。在原核和真核细胞中已经证明了许多在各种应激条件下 D-氨基酸积累的例子。在这项工作中，我们使野生型大肠杆菌和消化系统成员受到碳和氮饥饿应激。使用 NMR 和 LC-MS 技术，我们首次发现 D-谷氨酸在应激细菌中积累，但在对照细胞中没有积累。这些结果以及现有的知识，使我们能够对 ALS 发展的途径提出新的见解：由压力微生物组产生的 D-谷氨酸诱导补体系统 C1q 上的神经生物化学通讯错误。证明这一观点可能对预防肌萎缩侧索硬化症等现代疾病如 ALS、阿尔茨海默病和帕金森病具有重要意义。
