Chen Mengdi, Zhang Yu, Hou Liyan, Zhao Zirui, Tang Peiyan, Sun Qingquan, Zhao Jie, Wang Qingshan
National-Local Joint Engineering Research Center for Drug-Research and Development (R&D) of Neurodegenerative Diseases, Dalian Medical University, Dalian, China.
Center of Genome and Personalized Medicine, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
NPJ Parkinsons Dis. 2025 Mar 6;11(1):43. doi: 10.1038/s41531-025-00892-6.
Strong evidence indicates that remodeling gut microbiota may be an effective approach to combat Parkinson's disease (PD). Scorpion Venom Heat-Resistant Synthesized Peptide (SVHRSP), a synthesized peptide discovered from scorpion venom, displays potent neuroprotection in multiple PD models. However, the potential mechanisms remain unclear. In this study, we demonstrated that SVHRSP effectively attenuated gastrointestinal function impairments and reinstated the microbiota composition in rotenone-induced PD mouse model. Microbiota depletion and FMT verified that the restored gut microbiota was necessary for SVHRSP-mediated neuroprotection against dopaminergic neurodegeneration in rotenone PD mice. Furthermore, SVHRSP gut microbiota-dependently attenuated BBB impairment, microglial activation, and gene expression of pro-inflammatory factors in rotenone-treated mice. Mechanistically, SVHRSP decreased the concentrations of LPS and HMGB1 in both serum and brain tissue, thereby inhibiting the TLR4/NF-κB signaling pathway in the brain of rotenone-treated mice. Together, our findings provided fresh perspectives on the mechanisms underlying SVHRSP-induced neuroprotection in PD.
有力证据表明，重塑肠道微生物群可能是对抗帕金森病（PD）的有效方法。蝎毒耐热合成肽（SVHRSP）是一种从蝎毒中发现的合成肽，在多个PD模型中显示出强大的神经保护作用。然而，其潜在机制仍不清楚。在本研究中，我们证明SVHRSP有效减轻了鱼藤酮诱导的PD小鼠模型中的胃肠功能障碍，并恢复了微生物群组成。微生物群耗竭和粪菌移植证实，恢复的肠道微生物群是SVHRSP介导的对鱼藤酮诱导的PD小鼠多巴胺能神经变性的神经保护所必需的。此外，SVHRSP在肠道微生物群依赖的情况下减轻了鱼藤酮处理小鼠的血脑屏障损伤、小胶质细胞激活和促炎因子的基因表达。从机制上讲，SVHRSP降低了血清和脑组织中LPS和HMGB1的浓度，从而抑制了鱼藤酮处理小鼠大脑中的TLR4/NF-κB信号通路。总之，我们的研究结果为SVHRSP在PD中诱导神经保护的潜在机制提供了新的视角。
