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

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

机构地区：[1]Department of Pharmacology,Nanjing University of Chinese Medicine,Nanjing,210023,China [2]State Key Laboratory of Pharmaceutical Biotechnology,Institute of Functional Biomolecules,School of Life Sciences,Nanjing University,Nanjing,210023,China [3]Jiangsu Key Laboratory of Neurodegeneration,Department of Pharmacology,Nanjing Medical University,Nanjing,211116,China

出　　处：《Acta Pharmacologica Sinica》2024年第7期1366-1380,共15页中国药理学报（英文版）

基　　金：supported by grants from the National Natural Science Foundation of China (No.81991523,82003725);the National Key R&D Programme of China (No.2021ZD0202901).

摘　　要：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.

关 键 词：Parkinson's disease compound TAG lipid metabolism RUBCN 

分 类 号：R96[医药卫生—药理学]