title: (-)-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.affiliation: DME Center, Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong Province, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Chang
authors.affiliation: DME Center, Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong Province, China.
authors.forename: Cuiping
authors.initials: C
authors.lastname: Rong
authors.affiliation: DME Center, Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong Province, China; Department of Encephalopathy, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510080, Guangdong Province, China.
authors.forename: Yunbo
authors.initials: Y
authors.lastname: Chen
authors.affiliation: DME Center, Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong Province, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Oncology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou 510120, Guangdong Province, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Hu
authors.affiliation: DME Center, Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong Province, China.
authors.forename: Yousheng
authors.initials: Y
authors.lastname: Mo
authors.affiliation: DME Center, Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong Province, China.
authors.forename: Chunxia
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Guangzhou Women and Children׳s Medical Center, Guangzhou 510623, China.
authors.forename: Xiaoqiong
authors.initials: X
authors.lastname: Gu
authors.affiliation: DME Center, Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong Province, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: DME Center, Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong Province, China.
authors.forename: Wenqing
authors.initials: W
authors.lastname: He
authors.affiliation: DME Center, Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong Province, China; Department of Encephalopathy, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510080, Guangdong Province, China.
authors.forename: Shuyi
authors.initials: S
authors.lastname: Cheng
authors.affiliation: DME Center, Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong Province, China.
authors.forename: Xueqin
authors.initials: X
authors.lastname: Hou
authors.affiliation: DME Center, Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong Province, China.
authors.forename: Ruyu
authors.initials: R
authors.lastname: Su
authors.affiliation: DME Center, Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong Province, China.
authors.forename: Sijun
authors.initials: S
authors.lastname: Liu
authors.affiliation: DME Center, Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong Province, China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Dun
authors.affiliation: DME Center, Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong Province, China; Department of Encephalopathy, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510080, Guangdong Province, China. Electronic address: 1055898390@qq.com.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: DME Center, Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong Province, China; Department of Encephalopathy, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510080, Guangdong Province, China. Electronic address: fshkm@126.com.
authors.forename: Shuhuan
authors.initials: S
authors.lastname: Fang
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D016466:CHO Cells; D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D049109:Cell Proliferation; D002478:Cells, Cultured; D003072:Cognition Disorders / Q000188:drug therapy* / Q000378:metabolism; D003412:Cricetulus; D004195:Disease Models, Animal; D051379:Mice; D015260:Neprilysin / Q000378:metabolism*; D013237:Stereoisomerism; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D002392:Catechin; C045651:epigallocatechin gallate; D015260:Neprilysin
keywords: (−)-Epigallocatechin-3-gallate; Alzheimer׳s disease; Histone deacetylase inhibitor; Neprilysin; β-Amyloid