4‐Hydroxy‐2‐Nonenal Pyrrole Adducts in Human Neurodegenerative Disease
4‐Hydroxy‐2‐Nonenal Pyrrole Adducts in Human Neurodegenerative Disease
复制标题
4-羟基-2-壬醛吡咯加合物在人类神经退行性疾病中的作用
DOI：
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发表时间：
1997
影响因子：
3.2
通讯作者：
T. Montine
中科院分区：
文献类型：
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作者：
K. Montine;P. Kim;S. Olson;W. Markesbery;T. Montine
年龄增长和载脂蛋白E（APOE 4）ε 4等位基因的遗传是散发性和迟发性家族性阿尔茨海默病（AD）的重要危险因素;然而，导致AD的机制尚不清楚。许多研究已经将年龄的增长与对大脑的氧化挑战指数的增加以及AD患者相关大脑区域的氧化损伤的进一步增加相关联。脑氧化损伤的主要后果是脂质过氧化，产生神经毒性代谢物4-羟基-2-壬烯醛（HNE）。HNE与蛋白质反应产生几种加合物，包括在生物系统中不可逆形成的吡咯加合物。以前，我们已经表明，在少数AD和对照组患者中，HNE吡咯加合物抗血清与神经元缠结（NFT）呈免疫反应性，并且这种反应性与APOE 4的遗传显著相关。其他人已经证实了AD脑中的这种免疫反应性模式，但没有观察到与APOE 4的关联。在此，我们将研究组扩大到19名APOE 4或APOE 3纯合子AD患者，以及30名患有其他神经退行性疾病的患者，包括弥漫性路易体病，皮克病，进行性核上性麻痹，帕金森病和人类免疫缺陷病毒-1脑炎。AD患者NFT上的HNE吡咯加合物免疫反应性与APOE 4纯合性密切相关。除了罕见的免疫反应性皮克体在皮克氏病的情况下，没有其他结构被识别的HNE吡咯加合物抗血清在这一系列的患者。我们建议，有一个显着的差异之间的相互作用apoE 3和apoE 4与脂质过氧化作用的AD患者的大脑。
Increasing age and inheritance of the ∈4 allele of apolipoprotein E (APOE4) are significant risk factors for sporadic and late onset familial Alzheimer disease (AD); however, the mechanisms by which either leads to AD are unknown. Numerous studies have associated advancing age with increased indices of oxidative challenge to brain, and with still further increased oxidative damage to relevant brain regions in AD patients. A major consequence of oxidative damage to brain is lipid peroxidation with production of the neurotoxic metabolite 4-hydroxy-2-nonenal (HNE). HNE reacts with protein to yield several adducts, including a pyrrole adduct that forms irreversibly in biological systems. Previously, we have shown in a small number of AD and control patients that HNE pyrrole adduct antiserum is immunoreactive with neurofibrillary tangles (NFT), and that this reactivity was significantly associated with inheritance of APOE4. Others have confirmed this pattern of immunoreactivity in AD brain but did not observe an association with APOE4. Herein, we have expanded the study group to 19 AD patients homozygous for APOE4 or APOE3, as well as 30 patients with other neurodegenerative diseases, including diffuse Lewy body disease, Pick's disease, progressive supranuclear palsy, Parkinson's disease, and human immunodeficiency virus-1 encephalitis. HNE pyrrole adduct immunoreactivity on NFT in AD patients was strongly associated with APOE4 homozygosity. With the exception of rare immunoreactive Pick bodies in one case of Pick's disease, no other structure was recognized by HNE pyrrole adduct antiserum in this series of patients. We propose that there is a significant difference between the interaction of apoE3 and apoE4 with lipid peroxidation in the brains of AD patients.