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

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.