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

Exp Cell Res. 2015 May 15;334(1):136-45. doi: 10.1016/j.yexcr.2015.04.004. Epub 2015 Apr 14.

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.

Keywords: (−)-Epigallocatechin-3-gallate; Alzheimer׳s disease; Histone deacetylase inhibitor; Neprilysin; β-Amyloid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Catechin
  • epigallocatechin gallate
  • Neprilysin