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病理性tau蛋白的N-聚糖分析:阿尔茨海默病中tau蛋白异常加工的可能发生情况

Analysis of N-glycans of pathological tau: possible occurrence of aberrant processing of tau in Alzheimer's disease.

作者信息

Sato Y, Naito Y, Grundke-Iqbal I, Iqbal K, Endo T

机构信息

Department of Glycobiology, Tokyo Metropolitan Institute of Gerontology, Japan.

出版信息

FEBS Lett. 2001 May 11;496(2-3):152-60. doi: 10.1016/s0014-5793(01)02421-8.

DOI:10.1016/s0014-5793(01)02421-8
PMID:11356201
Abstract

In a previous study [Wang et al. (1996) Nat. Med. 2, 871-875], Wang et al. found (i) that abnormally hyperphosphorylated tau (AD P-tau) isolated from Alzheimer's disease (AD) brain as paired helical filaments (PHF)-tau and as cytosolic AD P-tau but not tau from normal brain were stained by lectins, and (ii) that on in vitro deglycosylation the PHF untwisted into sheets of thin straight filaments, suggesting that tau only in AD brains is glycosylated. To elucidate the primary structure of N-glycans, we comparatively analyzed the N-glycan structures obtained from PHF-tau and AD P-tau. More than half of N-glycans found in PHF-tau and AD P-tau were different. High mannose-type sugar chains and truncated N-glycans were found in both taus in addition to a small amount of sialylated bi- and triantennary sugar chains. More truncated glycans were richer in PHF-tau than AD P-tau. This enrichment of more truncated glycans in PHF might be involved in promoting the assembly and or stabilizing the pathological fibrils in AD.

摘要

在之前的一项研究中[Wang等人(1996年),《自然医学》2,871 - 875页],Wang等人发现:(i)从阿尔茨海默病(AD)脑部分离出的异常高度磷酸化的tau(AD P-tau),以成对螺旋丝(PHF)-tau和胞质AD P-tau的形式存在,但正常脑的tau未被凝集素染色;(ii)在体外去糖基化时,PHF解旋成薄直丝片,这表明只有AD脑中的tau被糖基化。为了阐明N-聚糖的一级结构,我们比较分析了从PHF-tau和AD P-tau获得的N-聚糖结构。在PHF-tau和AD P-tau中发现的超过一半的N-聚糖是不同的。除了少量的唾液酸化二天线和三天线糖链外,在两种tau中都发现了高甘露糖型糖链和截短的N-聚糖。PHF-tau中的截短聚糖比AD P-tau中的更丰富。PHF中这种更丰富的截短聚糖可能参与促进AD中病理性原纤维的组装和/或稳定。

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