(-)-Epigallocatechin-3-gallate attenuates cognitive deterioration in Alzheimer's disease model mice by upregulating neprilysin expression.

Abstract

Epigenetic changes are involved in learning and memory, and histone deacetylase (HDAC) inhibitors are considered potential therapeutic agents for Alzheimer's disease (AD). We previously reported that (-)-epigallocatechin-3-gallate (EGCG) acts as an HDAC inhibitor. Here, we demonstrate that EGCG reduced β-amyloid (Aβ) accumulation in vitro and rescued cognitive deterioration in senescence-accelerated mice P8 (SAMP8) via intragastric administration of low- and high-dose EGCG (5 and 15 mg/kg, respectively) for 60 days. The AD brain has decreased levels of the rate-limiting degradation enzyme of Aβ, neprilysin (NEP). We found an association between EGCG-induced reduction in Aβ accumulation and elevated NEP expression. Further, NEP silencing prevented the EGCG-induced Aβ downregulation. Our findings suggest that EGCG might be effective for treating AD.

• Authors: Xiang Chang, Cuiping Rong, Yunbo Chen, Cong Yang, Qian Hu, Yousheng Mo, Chunxia Zhang, Xiaoqiong Gu, Lei Zhang, Wenqing He, Shuyi Cheng, Xueqin Hou, Ruyu Su, Sijun Liu, Wenjun Dun, Qi Wang, Shuhuan Fang
• Journal: Experimental cell research (Exp Cell Res) Vol. 334 Issue 1 Pg. 136-45 (May 15 2015) ISSN: 1090-2422 [Electronic] United States
• PMID: 25882496 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Catechin
• epigallocatechin gallate
• Neprilysin

Topics

• Alzheimer Disease (drug therapy, metabolism)
• Animals
• CHO Cells
• Catechin (analogs & derivatives, chemistry, pharmacology)
• Cell Proliferation
• Cells, Cultured
• Cognition Disorders (drug therapy, metabolism)
• Cricetulus
• Disease Models, Animal
• Mice
• Neprilysin (metabolism)
• Stereoisomerism
• Up-Regulation (drug effects)