AMI, an Indazole Derivative, Improves Parkinson’s Disease by Inhibiting Tau Phosphorylation

Frontiers in Molecular Neuroscience

Yu Hui¹  Zhang Mao²  Xu Jiang-ping²  Wang Wen-ya²  Wang Hai-tao²  Lan Shi-yi²  Zhu Wen-ting³ 

[1] School of Basic Medical Science, Southern Medical University, Guangzhou, China.;School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China;The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China;

关键词: 6-amino-1-methyl-indazole;    Parkinson’s disease;    tau;    SH-SY5Y;    MPTP;   

DOI  :  10.3389/fnmol.2020.00165

来源: DOAJ

【 摘 要 】

Dopaminergic neuronal loss is the main pathological character of Parkinson’s disease (PD). Abnormal tau hyperphosphorylation will lead to dopaminergic neuronal loss. An indazole derivative 6-amino-1-methyl-indazole (AMI) successfully synthesized to inhibit tau hyperphosphorylation may exert a neuroprotective effect. The in vitro study showed that AMI effectively increased cell viability and alleviated the apoptosis induced by MPP+ in SH-SY5Y cells. In addition, AMI treatment significantly decreased the expression of p-tau and upstream kinases GSK-3β. In the MPTP-induced PD mice models, we found AMI apparently preserved dopaminergic neurons in the substantia nigra and improved the PD behavioral symptoms. Our results demonstrate that AMI exerts a neuroprotective effect by inhibiting tau hyperphosphorylation, representing a promising new candidate for PD treatment.

【 授权许可】

Unknown