Ginkgolic acid inhibited Tau phosphorylation and improved cognitive ability through the SUMO-1/GSK3β pathway in Aβ-Induced Alzheimer’s disease model rats

[Display omitted] •Ginkgolic acid (GA) possessed protective effects on cognitive impairment of Aβ-induced AD rat model.•GA suppressed neuronal apoptosis and oxidative stress induced by Aβ1-42 both in vivo and in vitro.•GA significantly inhibited Tau phosphorylation, and blocked the activation of SUMO-1/GSK3β signaling pathway. Alzheimer’s disease (AD) is a progressive neurological disorder, with two main pathological hallmarks of senile plaques and neurofibrillary tangles accumulated of abnormally phosphorylated Tau. Ginkgolic acid (GA), as an inhibitor of SUMO-1, exhibits many biological activities, including neuroprotective effects. However, the efficacy of GA in AD treatment has not been sufficiently investigated. Therefore, the current study aimed to explore the function and the underlying molecular mechanisms of GA related to AD. Our study revealed that GA exerted protective effects on cognitive impairment of an Aβ-induced AD rat model, and suppressed the neuronal apoptosis and oxidative stress induced by Aβ1-42 both in vivo and in vitro. Of crucial importance, GA significantly inhibited Tau phosphorylation, and blocked the activation of the SUMO-1/GSK3β signaling pathway. Taken together, these observations demonstrated that GA improved cognitive ability and inhibited Tau phosphorylation through SUMO1/GSK3β pathway, indicating that GA is a potential drug for the preventing and treatment of AD.