文献类型：期刊文献

英文题名：Expression and functional profiling of neprilysin, insulin-degrading enzyme, and endothelin-converting enzyme in prospectively studied elderly and Alzheimer's brain

作者：Wang, Suqing[1,2];Wang, Rui[1,3];Chen, Lang[1];Bennett, David A.[4];Dickson, Dennis W.[5];Wang, Deng-Shun[1]

机构：[1]Univ Wisconsin, Sch Med & Publ Hlth, Dept Pathol & Lab Med, Madison, WI 53705 USA;[2]Wuhan Univ, Sch Publ Hlth, Dept Nutr & Food Hlth, Wuhan 430072, Peoples R China;[3]E China Univ Sci & Technol, Sch Pharm, Dept Pharmaceut Sci, Shanghai 200237, Peoples R China;[4]Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA;[5]Mayo Clin, Coll Med, Dept Pathol Neuropathol & Neurosci, Jacksonville, FL 32224 USA

年份：2010

卷号：115

期号：1

起止页码：47

外文期刊名：JOURNAL OF NEUROCHEMISTRY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000281828200005)】；

基金：This work is supported by NIH grants AG025722 and AG029972 (to DSW), and an Alzheimer Association Grant IIRG-08-90524 (to DSW), and the start fund from the Department of Pathology and Laboratory Medicine, University of Wisconsin and Public Health, Madison, Wisconsin (to DSW), and NIH grants to DWD and P30AG10161 and R01AG15819 (to D. A. B.).

语种：英文

外文关键词：Alzheimer's disease; Alzheimer's disease brain; amyloid-degrading enzymes; degradation; endothelin-converting enzyme; insulin-degrading enzyme; neprilysin; beta-amyloid

摘要：P>The brain steady state level of beta-amyloid (A beta) is determined by the balance between its production and removal, the latter through egress across blood and CSF barriers as well as A beta degradation. The major A beta-degrading enzymes are neprilysin (NEP), insulin-degrading enzyme (IDE), and endothelin-converting enzyme (ECE-1). Although evidence suggests that NEP is down-regulated in Alzheimer's disease (AD), the role of IDE and ECE in the A beta accumulation in aging and dementia remains less certain. In this study, we examined mRNA and protein expression, as well as biological activity of NEP, IDE, and ECE-1 in human frontal cortex by real-time RT-PCR for mRNA, immunoblotting for protein, and highly sensitive and specific fluorescence assays for activity. The relationships between A beta-degrading enzymes and pathologic measures and clinical features were also assessed. The results showed that NEP mRNA, protein level, and activity were decreased in AD compared with normal controls with no cognitive impairment (NCI). In contrast, IDE activity was unchanged, but there was higher expression of IDE mRNA, indicating a possible compensatory reaction because of deficits in activity. ECE-1 expression in AD brain showed no significant difference compared with age-matched controls. Correlation analyses suggested that NEP expression was correlated with A beta accumulation and clinical diagnosis, being lower in AD than in no cognitive impairment. In contrast, neither IDE nor ECE-1 correlated with A beta or clinical diagnosis. These findings provide additional support for NEP as the major protease involved in A beta degradation and suggest its possible therapeutic targeting in AD.