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轻度认知障碍和阿尔茨海默病中 NEP2 表达和活性的改变。

Altered NEP2 expression and activity in mild cognitive impairment and Alzheimer's disease.

机构信息

Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USA.

出版信息

J Alzheimers Dis. 2012;28(2):433-41. doi: 10.3233/JAD-2011-111307.

DOI:10.3233/JAD-2011-111307
PMID:22008264
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3320721/
Abstract

Neprilysin-2 (NEP2), a close homolog of neprilysin (NEP), degrades amyloid-β (Aβ) and serves an important role in clearing Aβ in vivo. We measured NEP2 and NEP mRNA levels from non-impaired (NI), mild cognitive impaired (MCI), and clinical Alzheimer's disease (AD) subjects in the mid-temporal gyrus, mid-frontal gyrus, caudate, and cerebellum. NEP2 activity levels were also determined. Our results indicate that NEP2 and NEP mRNA expression is altered in MCI subjects relative to NI subjects in AD-susceptible regions. NEP2 enzymatic activity was lowered in association with MCI and AD and was positively associated with cognitive function, independent of diagnostic category. Our finding that NEP2 expression and activity are altered in MCI is significant as these changes may potentially serve as preclinical markers for AD and reduced NEP2 activity may be associated with the development of AD.

摘要

脑啡肽酶 2(NEP2)是脑啡肽酶(NEP)的近缘同源物,可降解淀粉样蛋白-β(Aβ),并在体内清除 Aβ 中发挥重要作用。我们测量了来自非损伤(NI)、轻度认知障碍(MCI)和临床阿尔茨海默病(AD)患者的中颞叶、中额叶、尾状核和小脑的 NEP2 和 NEP mRNA 水平。还测定了 NEP2 活性水平。我们的结果表明,与非损伤对照相比,NEP2 和 NEP mRNA 表达在 AD 易感区域的 MCI 患者中发生改变。NEP2 酶活性与 MCI 和 AD 相关降低,与认知功能呈正相关,与诊断类别无关。我们发现,在 MCI 中 NEP2 的表达和活性发生改变,这是有意义的,因为这些变化可能潜在地作为 AD 的临床前标志物,而 NEP2 活性降低可能与 AD 的发展有关。

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本文引用的文献

1
Neprilysin protects against cerebral amyloid angiopathy and Aβ-induced degeneration of cerebrovascular smooth muscle cells.脑啡肽酶可预防脑淀粉样血管病和 Aβ诱导的脑血管平滑肌细胞变性。
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Neprilysin-2 is an important β-amyloid degrading enzyme.脑啡肽酶 2 是一种重要的β-淀粉样蛋白降解酶。
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Decreased clearance of CNS beta-amyloid in Alzheimer's disease.阿尔茨海默病患者中枢神经系统β-淀粉样蛋白清除减少。
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Accumulation of insoluble amyloid-β in down's syndrome is associated with increased BACE-1 and neprilysin activities.唐氏综合征中不溶性淀粉样β的积累与 BACE-1 和 Neprilysin 活性的增加有关。
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Expression and functional profiling of neprilysin, insulin-degrading enzyme, and endothelin-converting enzyme in prospectively studied elderly and Alzheimer's brain.前瞻性研究老年和阿尔茨海默病大脑中脑啡肽酶、胰岛素降解酶和内皮素转换酶的表达和功能谱。
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Neprilysin and insulin-degrading enzyme levels are increased in Alzheimer disease in relation to disease severity.在阿尔茨海默病中,中性内肽酶和胰岛素降解酶水平随疾病严重程度增加。
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Validation of housekeeping genes for quantitative real-time PCR in in-vivo and in-vitro models of cerebral ischaemia.用于脑缺血体内和体外模型定量实时PCR的管家基因验证
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