Identification of a novel aromatic-turmerone analog that activates chaperone-mediated autophagy through the persistent activation of p38

• DOI: 10.3389/fcell.2024.1418296
• Publication Date: 2024-08-08T04:37:39Z
• Authors: Kensuke Motomura; Erika Ueda; Alex Boateng; Masaharu Sugiura; Keiichi Kadoyama; Natsuko Hitora-Im...; Yuki Kurauchi; Hiroshi Katsuki; Takahiro Seki
• Keywords: Chaperone (clinical); Identification

Introduction: Aromatic (Ar)-turmerone is a bioactive component of turmeric oil obtained from Curcuma longa . We recently identified novel analog (A2) ar-turmerone that protects dopaminergic neurons toxic stimuli by activating nuclear factor erythroid 2-related 2 (Nrf2). D-cysteine increases Nrf2, leading to the activation chaperone-mediated autophagy (CMA), pathway in autophagy-lysosome protein degradation system, primary cultured cerebellar Purkinje cells. In this study, we attempted identify analogs activate Nrf2 more potently and investigated whether these CMA. Methods: Four (A4–A7) A2 were synthesized. effects 4 on expression via immunoblotting CMA activity fluorescence observation. Results: Although all analogs, including A2, increased expression, only A4 activated SH-SY5Y Additionally, A4-mediated was not reversed inhibition, indicating mechanisms other than activation. focused p38, which participates Inhibition p38 significantly prevented phosphorylation 6 h after drug treatment, 24 treatment. Finally, revealed protected cells cytotoxicity rotenone, protection inhibiting p38. Conclusion: These findings suggest analog, A4, activates through persistent