南京中医药大学Gang Hu和南京大学Ren-xiang Tan共同合作，近期取得重要工作进展。他们研究提出，海洋来源化合物TAG可通过恢复RUBCN介导的脂质代谢稳态来缓解帕金森病。相关研究成果2024年3月27日在线发表于《药理学报》杂志上。

据介绍，帕金森病（PD）是第二常见的神经退行性疾病，其发病率正在上升。目前，尚无有效的治疗PD的方法。海洋来源的天然化合物因其独特的结构和多样的活性，而被认为是发现新药的重要资源。

研究人员发现，从海绵中分离出的聚酮TAG（tetrahydroauroglaucin）对MPTP/MPP⁺诱导的神经毒性具有显著的神经保护作用。RNA测序分析和代谢组学显示TAG显著改善PD模型中的脂质代谢紊乱。进一步的研究表明，TAG显著减少了脂滴（LD）的积累，下调了RUBCN的表达，并促进了自噬流。

此外，条件性敲低Rubcn显著减轻了PD样症状和LD的积累，同时阻断了TAG的神经保护作用。

总之，这一研究结果首次表明，TAG是一种有前景的PD治疗候选药物，可以通过RUBCN自噬途径抑制LD的积累，这为PD治疗提供了一种有效的新策略。

附：英文原文

Title: The marine-derived compound TAG alleviates Parkinson’s disease by restoring RUBCN-mediated lipid metabolism homeostasis

Author: Yang, Pei, Liu, Yang, Tong, Zhi-wu, Huang, Qian-hui, Xie, Xia-hong, Mao, Shi-yu, Ding, Jian-hua, Lu, Ming, Tan, Ren-xiang, Hu, Gang

Issue&Volume: 2024-03-27

Abstract: Parkinson’s disease (PD) is the second most common neurodegenerative disease, and its prevalence is increasing. Currently, no effective therapies for PD exist. Marine-derived natural compounds are considered important resources for the discovery of new drugs due to their distinctive structures and diverse activities. In this study, tetrahydroauroglaucin (TAG), a polyketide isolated from a marine sponge, was found to have notable neuroprotective effects on MPTP/MPP+-induced neurotoxicity. RNA sequencing analysis and metabolomics revealed that TAG significantly improved lipid metabolism disorder in PD models. Further investigation indicated that TAG markedly decreased the accumulation of lipid droplets (LDs), downregulated the expression of RUBCN, and promoted autophagic flux. Moreover, conditional knockdown of Rubcn notably attenuated PD-like symptoms and the accumulation of LDs, accompanied by blockade of the neuroprotective effect of TAG. Collectively, our results first indicated that TAG, a promising PD therapeutic candidate, could suppress the accumulation of LDs through the RUBCN-autophagy pathway, which highlighted a novel and effective strategy for PD treatment.

DOI: 10.1038/s41401-024-01259-y

Source: https://www.nature.com/articles/s41401-024-01259-y