EGCG: A Novel Therapeutic, Natural Product Inhibiting CDK5-Mediated Phosphorylation of CRMP-2 and Tau in Alzheimer’s Disease

Overview

Alzheimer’s disease is a neurodegenerative disorder characterized by the hyperphosphorylation of Tau and collapsin response mediator protein (CRMP -2), a newly identified Alzheimer’s signaling pathway protein. Hyperphosphorylation of these proteins is cause d by deregulated cyclin-dependent kinase-5 (CDK5) protein function. This increased phosphorylation activity leads to neurofibrillary tangles (NFTs), composed of hyperphosphorylated Tau and CRMP-2, leading to a loss in neuronal synaptic communication. Thus, all three proteins are potential targets to alleviate the impacts of Alzheimer’s. There is a lack of consensus on the molecular basis of Alzheimer’s, leading to inadequate treatment. Epigallocatechin -3 gallate (EGCG), a catechin found in green tea, has neuroprotective properties against inflammation of neural tissue and is an emerging medicinal herb with promising results. This paper explores the molecular interactions of proteins involved in Alzheimer’s and hypothesizes that EGCG may impede such interacti ons. To examine EGCG’s effects on key Alzheimer’s proteins, binding affinities between CRMP -2, CDK5, and Tau were characterized in the presence or absence of EGCG, using microscale thermophoresis (MST). The results indicated that EGCG decreased the binding affinities between the proteins. Kinase assays were conducted to uncover the impact on CDK5’s phosphorylation, revealing that the addition of CRMP-2 or Tau to CDK5 increased CDK5’s phosphorylation of Tau and CRMP-2. However, the addition of EGCG to the CR MP-2-CDK5 mixture and EGCG to the Tau-CDK5 mixture moderately decreased CDK5’s activity. Computational studies were conducted to determine binding sites and corroborate the binding results. Overall, the results suggest that EGCG could inhibit CDK5-mediated phosphorylation of Tau and CRMP-2.

Competition history

• JSHS 2025 Category not listed

Resources

• National JSHS abstract book ↗

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