title: Network Analysis of a Comprehensive Knowledge Repository Reveals a Dual Role for Ceramide in Alzheimer's Disease.
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.
authors: Department of Clinical Informatics, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.|Department of Clinical Record Informatics, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Miyagi, Japan.
authors: Satoshi
authors: S
authors: Mizuno
authors: Department of Clinical Record Informatics, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Miyagi, Japan.
authors: Soichi
authors: S
authors: Ogishima
authors: Department of Gynecology and Obstetrics, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors: Kazuyuki
authors: K
authors: Kitatani
authors: Department of Genome Informatics, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors: Masataka
authors: M
authors: Kikuchi
authors: Department of Clinical Record Informatics, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Miyagi, Japan.
authors: Hiroshi
authors: H
authors: Tanaka
authors: Department of Gynecology and Obstetrics, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors: Nobuo
authors: N
authors: Yaegashi
authors: Department of Clinical Informatics, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors: Jun
authors: J
authors: Nakaya
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000503:physiopathology; D002518:Ceramides / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D053858:Metabolic Networks and Pathways; D015398:Signal Transduction; D013107:Sphingolipids / Q000378:metabolism; D049490:Systems Biology / Q000379:methods
chemical_list: D002518:Ceramides; D018836:Inflammation Mediators; D013107:Sphingolipids