(-)-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.

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