In Silico Evaluation of the Role of Phytochemicals in Alzheimer's Disease Through Wnt Signaling Modulation

Abstract

Alzheimer’s disease (AD) is an irreversible, progressive and the most common reason for neurodegenerative disease. Wnt signaling plays important role during embryonic CNS development and is involved in neuronal induction, self-renewal, polarity, and synaptogenesis. Alteration in the Wnt Signaling pathway has been linked with age-related diseases like osteoporosis, colon cancer, Parkinson and AD. Several studies indicate that disruption of Wnt signaling particularly, canonical Wnt pathway contributes to AD pathogenesis. This study aims to evaluate the role of phytochemical in modulating Wnt signaling pathway by targeting the negative regulators of Wnt signaling. WIF1 (Wnt inhibitory factor 1) is the protein that binds to Wnt proteins making them unavailable and hence inhibiting the Wnt signaling. Low density lipoprotein receptor related protein 6 (Lrp6) is the co-receptor that along with Frizzled receptor is involved in the activation of Wnt signaling. Dickkopf 1(Dkk1) is the antagonist of Wnt signaling pathway that act by binding with LRP6 and leading to its degradation. Glycogen synthase kinase-3β (GSK-3 β) forms multimeric degradation complex that results in the degradation of β-catenin and inhibition of Wnt signaling pathway. All these four proteins are important targets for Wnt signaling inhibition that serves the purpose for modulating Wnt pathway.