Hyunji Jo
Ewha Womans University, South Korea
Title: The role of AMP-activated protein kinase as a novel therapeutic target for Alzheimer’s disease
Biography
Biography: Hyunji Jo
Abstract
Alzheimer’s Disease (AD) is an aging-associated neurodegenerative disease. AD patients suffer from behavioral deficits, mental distress and progressive memory impairments. Currently existing AD drugs are merely symptomatic treatments. Therefore, we need to find a novel therapeutic strategy for AD. Amyloid beta (Aβ), known as a marker of AD, is generated by cleaving Amyloid-Precursor Protein (APP) with β-secretase (BACE1) and γ-secretase. Identifying effective methods to suppress the Aβ accumulation has long been of great interest. Recently, AMP-Activated Protein Kinase (AMPK), a serine/threonine protein kinase, began to be focused as a novel therapeutic target since it has been reported to regulate formation of Aβ. Thus, in this study, 100 compounds were selected from screening a chemical library containing one million compounds by in silico study. We finally found YE-06 through chemical modifications and various bioassays. In accordance with the docking study, YE-06 potentially bound to the AMP binding site of AMPK. Compared to Metformin, which is a well-known AMPK activator, YE-06 significantly activated AMPK and consequently down-regulated the protein level of BACE1. The mRNA level of BACE1 was significantly reduced. We showed improvements in the cognition and movement coordination of AD rat model in YE-06 treated group through water maze test, probe test, passive avoidance test, rotarod test and vertical pole test. YE-06 efficiently increased ACh and decreased the AChE activity. Also, YE-06 significantly reduced neuronal cell death of AD rat models. Therefore, our results suggest that YE-06 is a potential compound for AD treatment.