Abstract
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.
Highlights
Alzheimer’s disease is the most common cause of senile dementia
18 review articles related to both sphingolipids and Alzheimer’s disease (AD) were collected and manually curated to update AlzPathway as ‘AlzPathway 3,’ using Cell Designer [22], a modeling editor for biochemical pathways
We collected 18 review articles related to both sphingolipids and AD, manually curated these review articles, and updated AlzPathway using Cell Designer ver. 4.2
Summary
Alzheimer’s disease is the most common cause of senile dementia. Nearly 36 million people were affected by dementia worldwide as of 2010, and this figure is estimated to increase to 65.7 million by 2030 [1]. A comprehensive knowledge repository was proposed to consider global connections among disease factors such as the relationships among signaling molecules, exposures, phenotypes and well-known but not well-understood factors including sphingolipids [11,12,13,14,15]. 18 review articles related to both sphingolipids and AD were collected and manually curated to update AlzPathway as ‘AlzPathway 3,’ using Cell Designer [22], a modeling editor for biochemical pathways.
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