Activation of caspase-6 in aging and mild cognitive impairment
Activation of caspase-6 in aging and mild cognitive impairment
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DOI：
10.2353/ajpath.2007.060974
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发表时间：
2007-04-01
影响因子：
6
通讯作者：
LeBlanc, Andrea C.
中科院分区：
文献类型：
--
作者：
Albrecht, Steffen;Bourdeau, Martine;LeBlanc, Andrea C.
在终末期阿尔茨海默病(AD)中，活性半胱氨酸氨基转移酶6(CSP6)和被CSP6裂解的Tau蛋白(Tau Delta CSP6)在神经炎性斑块(NPs)、神经纤维丝(NPTs)和神经原纤维缠结(NFTs)中大量存在(郭H，Albrecht S，Bourdeau)。M，Petzke T，Bergeron C，LeBlanc AC：活性caspase-6和caspase-6在阿尔茨海默病的神经纤维线、神经炎斑块和神经原纤维缠结中裂解Tau。AM J Pathol 2004,165：523-531)。这项研究的目的是确定CSP6是否存在于青年和老年非认知损害(NCI)、老年轻度认知损害(MCI)和老年疯狂、中度、重度和极重度AD患者中。用抗p2oCsp6和Tau Delta Csp6免疫反应评价Csp6活性。在AD的所有阶段，NFT、NPT和NP中都存在活性CSP6。活性CSP6存在于所有MCI病例的NFT中，并存在于某些MCI病例的NPT和NPs中。活性CSP6在所有NCI病例的NFT和NPT中都存在，但在年轻病例中缺失。在NCI个体中，Tau Delta Csp6阳性的NFT和NPT水平与总体认知得分呈负相关。因此，Csp6活性可在无AD的情况下随着年龄的增长而发生，并且总是与确诊的AD患者的临床和病理特征有关。鉴于活性CSP6能够增加淀粉样β蛋白的产生并裂解Tau和几种突触蛋白(LeBlanc AC、Liu H、Goodyer C、Bergeron C、Hammond J：caspase-6)，因此Cspase-6在人类神经细胞凋亡、淀粉样变和阿尔茨海默病中扮演着重要的角色。生物化学杂志，1999,274：2342623436；Petzke TL，Rousselet E，Goodyer C，LeBlanc AC：Caspase-6底物在人类原代神经元中的蛋白质组学研究。节目编号：80.9。2005摘要查看器/行程计划器。华盛顿特区：神经科学学会。在线)，我们认为活跃的Csp6可能是神经元功能障碍的早期启动者。
Active caspase-6 (Csp6) and Tau cleaved by Csp6 (Tau Delta Csp6) are abundant in neuritic plaques (NPs) , neuropil threads (NPTs), and neurofibrillary tangles (NFTs) in end-stage Alzheimer's disease (AD) (Guo H, Albrecht S, Bourdeau. M, Petzke T, Bergeron C, LeBlanc AC: Active caspase-6 and caspase-6 cleaved Tau in neuropil threads, neuritic plaques and neurofibrillary tangles of Alzheimer's disease. Am J Pathol 2004, 165:523-531). The goal of this study was to determine whether active Csp6 is present in young and aged noncognitively impaired (NCI); aged mild cognitively impaired (MCI); and aged mad, moderate, severe, and very severe AD individuals. Csp6 activity was assessed with anti-p2oCsp6 and Tau Delta Csp6 immunoreactivity. Active Csp6 is present in NFTs, NPTs, and NPs at all stages of AD. Active Csp6 is present in NFTs of all MCI cases and present in NPTs and NPs of some MCI cases. Active Csp6 is present in NFTs and NPTs of all NCI cases but is absent in younger cases. The level of Tau Delta Csp6-positive NFTs and NPTs correlates inversely with global cognitive scores in NCI individuals. Therefore, Csp6 activity can occur with aging in the absence of AD and is always associated with clinical and pathological features of confirmed AD cases. Given the ability of active Csp6 to increase amyloid-beta peptide production and cleave Tau and several synaptic proteins (LeBlanc AC, Liu H, Goodyer C, Bergeron C, Hammond J: Caspase-6 role in apoptosis of human neurons, amyloidogenesis and Alzheimer's disease. J Biol Chem 1999, 274:2342623436; Petzke TL, Rousselet E, Goodyer C, LeBlanc AC: Substrates of caspase-6 in human primary neurons: a proteomic study. Program No. 80.9. 2005 Abstract Viewer/Itinerary Planner. Washington, DC: Society for Neuroscience. Online), we suggest that active Csp6 could be an early instigator of neuronal dysfunction.