Activation of Wnt/β-Catenin Pathway by Icarisid II Improves Cognition

Abstract

Reestablishing the impaired neurogenesis in Alzheimer’s disease (AD) patients can lead to improved cognitive function. Xiao and colleagues investigated whether the natural product icarisid II (ICS II) which possesses strong neuroprotective properties can restore physiological neurogenesis in APP/PS1 mice. After oral administration of ICS II, APP/PS1 mice showed hippocampal neuronal generation alongside the activation Wnt/β-catenin signal pathway as exhibited by the stimulation of Wnt-3a, phosphorylated glycogen synthase kinase-3β (p-GSK-3β) and β-catenin. Their data also showed inhibition of phosphorylated dynamin-related protein 1 (p-Drp), mitochondrial fission factor (Mff), and mitochondrial fission 1 protein (Fis1). However, upregulation of Mitofusin 1 (Mfn 1) and Mitofusin (Mfn 2) suggested a depression in mitochondrial fission. These effects of ICS II were canceled by XAV-939. a Wnt/β-catenin signaling pathway inhibitor. The authors concluded that ICS II can mitigate mitochondrial fission through the Wnt/β-catenin pathway and alleviate cognitive damage through neurogenesis in an AD mouse model. Phytother Res. 2022 May;36(5):2095-2108.