Salsolinol as an RNA m~6A methylation inducer mediates dopaminergic neuronal death by regulating YAP1 and autophagy
作者机构:Beijing International Science and Technology Cooperation Base for Antiviral DrugsCollege of Chemistry and LifeBeijing University of TechnologyBeijingChina Department of RehabilitationBeijing Rehabilitation HospitalCapital Medical UniversityBeijingChina
出 版 物:《Neural Regeneration Research》 (中国神经再生研究(英文版))
年 卷 期:2025年第20卷第3期
页 面:887-899页
核心收录:
学科分类:1002[医学-临床医学] 100204[医学-神经病学] 10[医学]
基 金:supported by the National Natural Science Foundation of China,Nos.82271283(to XC),91854115(to JW),31970044(to JW) the Natural Science Foundation of Beijing,No.7202001(to XC) the Scientific Research Project of Beijing Educational Committee,No.KM202010005022(to XC)
主 题:ALKBH5 autophagy FTO Hippo pathway m~6A Parkinson's disease RNA methylation salsolinol YAP1 YTHDF2
摘 要:Salsolinol(1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline,Sal)is a catechol isoquinoline that causes neurotoxicity and shares structural similarity with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine,an environmental toxin that causes Parkinson s ***,the mechanism by which Sal mediates dopaminergic neuronal death remains *** this study,we found that Sal significantly enhanced the global level of N~6-methyladenosine(m~6A)RNA methylation in PC12 cells,mainly by inducing the downregulation of the expression of m~6A demethylases fat mass and obesity-associated protein(FTO)and alk B homolog 5(ALKBH5).RNA sequencing analysis showed that Sal downregulated the Hippo signaling *** m~6A reader YTH domain-containing family protein 2(YTHDF2)promoted the degradation of m~6A-containing Yes-associated protein 1(YAP1)mRNA,which is a downstream key effector in the Hippo signaling ***,downregulation of YAP1 promoted autophagy,indicating that the mutual regulation between YAP1 and autophagy can lead to *** findings reveal the role of Sal on m~6A RNA methylation and suggest that Sal may act as an RNA methylation inducer mediating dopaminergic neuronal death through YAP1 and *** results provide greater insights into the neurotoxic effects of catechol isoquinolines compared with other studies and may be a reference for assessing the involvement of RNA methylation in the pathogenesis of Parkinson s disease.