SUMO and Alzheimer's disease.
SUMO and Alzheimer's disease.
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相扑和阿尔茨海默氏病。
DOI：
10.1007/s12017-013-8257-7
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发表时间：
2013-12
影响因子：
3.5
通讯作者：
Fraser, Paul
中科院分区：
文献类型：
--
作者：
Lee, Linda;Sakurai, Mikako;Matsuzaki, Shinsuke;Arancio, Ottavio;Fraser, Paul
阿尔茨海默病（AD）是一种以进行性认知能力下降为特征的神经退行性疾病，是老年人痴呆的最常见原因。组织病理学上，AD的特点是大脑中淀粉样蛋白-β (Aβ)和微管相关蛋白tau的不溶性聚集，这两种蛋白都与小泛素样修饰物（SUMO）有关。大量的研究已经阐明了AD背后的许多分子和细胞途径，包括那些涉及异常Aβ和tau聚集的途径。然而，对该病的病因和发病机制的全面了解仍然是难以捉摸的。因此，目前没有有效的治疗选择可以改变疾病的进展，减缓或阻止认知功能的下降。作为解决这一缺陷的一部分，需要更好地理解在AD病理下受损的信号通路，包括通常控制这些网络的调节机制。其中一种机制涉及SUMOylation，这是一种翻译后修饰（PTM），参与调节细胞生物学的许多方面，也被发现具有几个关键的神经元特异性作用。早期研究表明，SUMO系统可能随着ad型病理而改变，这可能影响Aβ水平和tau聚集。尽管仍是一个相对未被探索的话题，但SUMOylation可能会以某种类似于其他调节性PTMs（如磷酸化）的方式成为AD发病机制的重要因素。因此，除了对tau和Aβ加工的上游影响外，还可能存在由Aβ聚集体或其他ad相关因子介导的下游影响sumo调节的信号通路。多种与AD病理相关的蛋白已被确定为SUMO底物，包括那些参与突触生理、线粒体动力学和炎症信号传导的蛋白。正在进行的研究将确定这些sumo调节的神经元和神经胶质细胞功能如何受到Aβ和AD病理的影响。在这里，我们回顾了目前关于SUMO参与AD的文献，并概述了SUMO化蛋白和AD发病机制中潜在失调的途径。
Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline and is the most common cause of dementia in the elderly. Histopathologically, AD features insoluble aggregates of two proteins in the brain, amyloid-β (Aβ) and the microtubule associated protein tau, both of which have been linked to the small ubiquitin-like modifier (SUMO). A large body of research has elucidated many of the molecular and cellular pathways that underlie AD, including those involving the abnormal Aβ and tau aggregates. However, a full understanding of the etiology and pathogenesis of the disease has remained elusive. Consequently, there are currently no effective therapeutic options that can modify the disease progression and slow or stop the decline of cognitive functioning. As part of the effort to address this lacking, there needs a better understanding of the signaling pathways that become impaired under AD pathology, including the regulatory mechanisms that normally control those networks. One such mechanism involves SUMOylation, which is a post-translational modification (PTM) that is involved in regulating many aspects of cell biology and has also been found to have several critical neuron-specific roles. Early studies have indicated that the SUMO system is likely altered with AD-type pathology, which may impact Aβ levels and tau aggregation. Although still a relatively unexplored topic, SUMOylation will likely emerge as a significant factor in AD pathogenesis in ways which may be somewhat analogous to other regulatory PTMs such as phosphorylation. Thus, in addition to the upstream effects on tau and Aβ processing, there may also be downstream effects mediated by Aβ aggregates or other AD-related factors on SUMO-regulated signaling pathways. Multiple proteins that have functions relevant to AD pathology have been identified as SUMO substrates, including those involved in synaptic physiology, mitochondrial dynamics and inflammatory signaling. Ongoing studies will determine how these SUMO-regulated functions in neurons and glial cells may be impacted by Aβ and AD pathology. Here, we present a review of the current literature on the involvement of SUMO in AD, as well as an overview of the SUMOylated proteins and pathways that are potentially dysregulated with AD pathogenesis.
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影响因子：
3.5
作者：
Chen H;Chan DC
通讯作者：
Chan DC
DOI：
10.1083/jcb.200712094
发表时间：
2008-07-14
期刊：
The Journal of cell biology
影响因子：
--
作者：
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通讯作者：
Hsueh YP
DOI：
10.1074/jbc.m112.356337
发表时间：
2012-06-29
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
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通讯作者：
Henley JM
影响因子：
168.9
作者：
Ballard, Clive;Gauthier, Serge;Jones, Emma
通讯作者：
Jones, Emma
影响因子：
4.7
作者：
Babu, JR;Geetha, T;Wooten, MW
通讯作者：
Wooten, MW