Network Analysis of a Comprehensive Knowledge Repository Reveals a Dual Role for Ceramide in Alzheimer's Disease.
Network Analysis of a Comprehensive Knowledge Repository Reveals a Dual Role for Ceramide in Alzheimer's Disease.
复制标题
DOI：
10.1371/journal.pone.0148431
复制
发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Nakaya J
中科院分区：
文献类型：
--
作者：
Mizuno S;Ogishima S;Kitatani K;Kikuchi M;Tanaka H;Yaegashi N;Nakaya J
阿尔茨海默病（Alzheimer's disease，AD）是老年性痴呆最常见的病因。已知许多炎症因子如淀粉样蛋白-β和促炎细胞因子有助于AD脑中的炎症反应。众所周知，鞘脂在炎性疾病的发病机制中具有作用，其中鞘脂在AD的炎症相关发病机制中的确切作用尚不清楚。在这里，我们进行了网络分析，以澄清鞘脂的重要性，并在AD炎症因子和鞘脂模型之间的关系。在这项研究中，我们更新了AD信号网络图中的鞘脂信号和代谢级联，我们将其命名为“AlzPathway”，这是AD信号通路的综合知识库。我们对更新的AlzPathway的网络分析表明，与神经酰胺相关的途径是主要途径之一，并且神经酰胺是AD发病机制的重要参与者之一。我们的分析结果提示了以下两个关于AD炎症的前景：（1）神经酰胺可能在AD的炎症和抗炎通路中发挥重要作用;（2）神经酰胺相关的炎症和抗炎通路可能与神经酰胺相关的因子如鞘磷脂酶和Siglec-11有关。在这项研究中，综合知识库的网络分析揭示了神经酰胺在AD中的双重作用。这一结果为阐明AD中鞘脂相关的炎症和抗炎通路提供了线索。
Alzheimer’s disease (AD) is the most common cause of senile dementia. Many inflammatory factors such as amyloid-β and pro-inflammatory cytokines are known to contribute to the inflammatory response in the AD brain. Sphingolipids are widely known to have roles in the pathogenesis of inflammatory diseases, where the precise roles for sphingolipids in inflammation-associated pathogenesis of AD are not well understood. Here we performed a network analysis to clarify the importance of sphingolipids and to model relationships among inflammatory factors and sphingolipids in AD. In this study, we have updated sphingolipid signaling and metabolic cascades in a map of AD signaling networks that we named “AlzPathway,” a comprehensive knowledge repository of signaling pathways in AD. Our network analysis of the updated AlzPathway indicates that the pathways related to ceramide are one of the primary pathways and that ceramide is one of the important players in the pathogenesis of AD. The results of our analysis suggest the following two prospects about inflammation in AD: (1) ceramide could play important roles in both inflammatory and anti-inflammatory pathways of AD, and (2) several factors such as Sphingomyelinase and Siglec-11 may be associated with ceramide related inflammation and anti-inflammation pathways in AD. In this study, network analysis of comprehensive knowledge repository reveals a dual role for ceramide in AD. This result provides a clue to clarify sphingolipids related inflammatory and anti-inflammatory pathways in AD.
影响因子：
3.7
作者：
Kwak JW;Jeong H;Han SH;Kim Y;Son SM;Mook-Jung I;Hwang D;Park JW
通讯作者：
Park JW