MONNA alleviates MPTP-induced Parkinson's disease in zebrafish by activating TFEB dependently on ER Calcium
文献类型：期刊论文
| 作者 | Tang, Meiqin9; Luo, Ting1,2; Kang, Chunlan2,9; Wang, Feng2,3; Yang, Dongqing2,3; Cui, Ruili2,4; Li, Chanjing2,9; Zhang, Yihan2,5,6; Liu, Yiyao2; Li, Min7 |
| 刊名 | CELL CALCIUM
 |
| 出版日期 | 2026-03-01 |
| 卷号 | 134页码:13 |
| 关键词 | MONNA Transcription factor EB (TFEB) a-synuclein autophagy |
| ISSN号 | 0143-4160 |
| DOI | 10.1016/j.ceca.2026.103125 |
| 通讯作者 | Hu, Mei(humei13@163.com) ; Li, Ping(lipingt@simm.ac.cn) |
| 英文摘要 | A-synuclein aggregation is a biomarker of Parkinson's disease (PD) whose feature is the progressive loss of dopaminergic neuron in the middle brain. The removal of a-synuclein aggregation through autophagy-lysosome pathway is a promising strategy for PD treatment. Transcription factor EB (TFEB) is a master regulator of autophagic and lysosomal biogenesis and function. Here, we report a library screen of intracellular Ca2+ inducers to identify small-molecule agonists of TFEB and discover MONNA can promote autophagic and lysosomal activity. Notably, MONNA facilitates the reduction of pathological a-synuclein in the Parkinson's disease model both in vitro and in vivo, and ameliorates PD-like behaviors in zebrafish. Mode of action studies reveal MONNA induces TFEB nuclear translocation through a Ca2+-dependent mechanism involving Calcineurin (CaN). Endoplasmic reticulum (ER) but not lysosome Ca2+ is critical to MONNA-induced TFEB activation and autophagy induction. Furthermore, Sarcoendoplasmic reticulum calcium ATPase (SERCA) pump of ER modulates TFEB nuclear translocation induced by MONNA. Our findings demonstrate that MONNA is the first ER Ca2+-dependent small synthetic TFEB agonist promoting the degradation of a-synuclein aggregates and alleviating Parkinson's disease. This ER Ca2+-Calcineurin-TFEB signaling pathway would broaden the way to develop drugs for PD. |
| WOS关键词 | AUTOPHAGY ; CA2+ ; NEURODEGENERATION ; MECHANISM ; CHANNELS ; PATHWAY ; STORES ; TRPML1 |
| 资助项目 | National Natural Science Foundation of China[82,273,913] ; National Natural Science Foundation of China[32,100,621] ; National Natural Science Foundation of China[82,504,682] ; Guangdong Basic and Applied Basic Research Foundation[2025B1515020003] ; Guangdong Basic and Applied Basic Research Foundation[2022A1515010851] ; Zhongshan Municipal Bureau of Science and Technology[220,418,134,367,984] ; Zhongshan Municipal Bureau of Science and Technology[CXTD2022013] ; Science and Technology Major Project of Zhongshan City, Guangdong Province[2023B3016] ; High-level new RD institute[2019B090904008] ; Medical Scientific Research Foundation of Guangdong Province of China[A2024048] ; Highlevel Innovative Research Institute from Department of Science and Technology of Guangdong Province[2021B0909050003] |
| WOS研究方向 | Cell Biology ; Physiology |
| 语种 | 英语 |
| WOS记录号 | WOS:001683978100001 |
| 出版者 | ELSEVIER SCI LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/322857]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Hu, Mei; Li, Ping |
| 作者单位 | 1.Guizhou Med Univ, Sch Pharmaceut Sci, Guiyang 550025, Peoples R China 2.Zhongshan Inst Drug Discovery, Zhongshan 528400, Peoples R China 3.Zunyi Med Univ, Sch Pharm, Zunyi 563000, Peoples R China 4.Nanjing Univ Chinese Med, Coll Pharm, Nanjing 210023, Peoples R China 5.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 6.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 7.First Peoples Hosp Datong, Dept Children Hlth Care, Datong 037000, Peoples R China 8.Guangzhou Univ Chinese Med, Zhongshan Tradit Chinese Med Hosp, Pharmacol Lab, Zhongshan 528401, Peoples R China 9.Southern Med Univ, Sch Pharmaceut Sci, Guangzhou 510515, Peoples R China |
| 推荐引用方式 GB/T 7714 | Tang, Meiqin,Luo, Ting,Kang, Chunlan,et al. MONNA alleviates MPTP-induced Parkinson's disease in zebrafish by activating TFEB dependently on ER Calcium[J]. CELL CALCIUM,2026,134:13. |
| APA | Tang, Meiqin.,Luo, Ting.,Kang, Chunlan.,Wang, Feng.,Yang, Dongqing.,...&Li, Ping.(2026).MONNA alleviates MPTP-induced Parkinson's disease in zebrafish by activating TFEB dependently on ER Calcium.CELL CALCIUM,134,13. |
| MLA | Tang, Meiqin,et al."MONNA alleviates MPTP-induced Parkinson's disease in zebrafish by activating TFEB dependently on ER Calcium".CELL CALCIUM 134(2026):13. |
入库方式： OAI收割
来源：上海药物研究所
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