Towards understanding the roles of heparan sulfate proteoglycans in Alzheimer's disease.
Towards understanding the roles of heparan sulfate proteoglycans in Alzheimer's disease.
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DOI：
10.1155/2014/516028
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发表时间：
2014
影响因子：
--
通讯作者：
Li JP
中科院分区：
文献类型：
--
作者：
Zhang GL;Zhang X;Wang XM;Li JP
阿尔茨海默病（AD）是最常见的痴呆症，其特征是记忆力逐渐丧失和认知功能障碍。阿尔茨海默病的中心病理事件是细胞毒性淀粉样蛋白-β肽（Aβ）在脑实质中的积累和沉积。硫酸肝素蛋白聚糖（HSPGs）和侧链硫酸肝素（HS）与AD患者和AD转基因动物模型中的Aβ沉积有关。体外和体内研究越来越多的证据表明，HSPG/HS在Aβ发病机制中的功能作用。尽管“HSPG/HS如何以及为什么与Aβ共沉积”的问题仍然存在，但了解这些事件的机制是可以实现的。免疫组化检查的最新进展揭示了HS与Aβ共沉积的分子结构。最近的一些报道为HSPG在Aβ发病机制中的作用提供了重要的新见解。特别是，小鼠模型实验显示HSPG在调节Aβ相关的神经炎症和大脑中Aβ的清除方面具有不可或缺的功能。应用分子干扰HS和Aβ肽之间的相互作用已证明对AD小鼠模型有益。阐明HSPG/HS在Aβ沉积和毒性中的功能有助于进一步了解AD的复杂病理。这一进展鼓励了针对hs - a - β相互作用的AD新治疗方法的开发。
Alzheimer's disease (AD) is the most common form of dementia, characterized by progressive loss of memory and cognitive dysfunctions. A central pathological event of AD is accumulation and deposition of cytotoxic amyloid-β peptide (Aβ) in the brain parenchyma. Heparan sulfate proteoglycans (HSPGs) and the side chains heparan sulfate (HS) are found associated with Aβ deposits in the brains of AD patients and transgenic animal models of AD. A growing body of evidence from in vitro and in vivo studies suggests functional roles of HSPG/HS in Aβ pathogenesis. Although the question of “how and why HSPG/HS is codeposited with Aβ?” still remains, it is within reach to understand the mechanisms of the events. Recent progress by immunohistochemical examination with advanced antibodies shed light on molecular structures of HS codeposited with Aβ. Several recent reports have provided important new insights into the roles of HSPG in Aβ pathogenesis. Particularly, experiments on mouse models revealed indispensible functions of HSPG in modulating Aβ-associated neuroinflammation and clearance of Aβ from the brain. Application of molecules to interfere with the interaction between HS and Aβ peptides has demonstrated beneficial effects on AD mouse models. Elucidating the functions of HSPG/HS in Aβ deposition and toxicity is leading to further understanding of the complex pathology of AD. The progress is encouraging development of new treatments for AD by targeting HS-Aβ interactions.
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影响因子：
6.9
作者：
Christianson, Helena C.;Belting, Mattias
通讯作者：
Belting, Mattias
影响因子：
14.8
作者：
Galvis, Martha L. Escobar;Jia, Juan;Li, Jin-Ping
通讯作者：
Li, Jin-Ping
影响因子：
4.8
作者：
Bame, KJ;Danda, J;Tumova, S
通讯作者：
Tumova, S
DOI：
10.1111/j.1750-3639.2008.00195.x
发表时间：
2009-10
期刊：
Brain pathology (Zurich, Switzerland)
影响因子：
--
作者：
Bonneh-Barkay D;Wiley CA
通讯作者：
Wiley CA
影响因子：
9.8
作者：
Campion, D;Dumanchin, C;Frebourg, T
通讯作者：
Frebourg, T