Computational analysis of potential off-target effects for non-steroidal anti-inflammatory drugs and their associations with Alzheimer''s disease / 利用生物資訊方法分析非類固醇抗發炎藥物潛在的脫靶效應及其與阿茲海默症的關聯

碩士 / 高雄醫學大學 / 藥學系碩士在職專班 / 104 / The NSAIDs (Nonsteroidal Anti-inflammatory Drugs) represent the single most crowded family of drugs sharing the same therapeutic activities and mechanism of action, but there were large interindividual variability in response to these agents. NSAIDs provide symptomatic relief of pain and inflammation associated with a variety of human disorders, including the rheumatic diseases, but NSAIDs can also cause serious side effects, including stomach ulcers, stomach bleeding and increased risk of atherothrombotic vascular events. The investigation of off-target effects of NSAIDs could provide better understanding of the adverse effects.
In this study, ChemDIS were utilized to identify the interaction proteins for NSAIDs and analyze chemical-associated Gene Ontology (GO), pathway (KEGG and Reactome) and Disease Ontology (DO and DOlite) of NSAIDs based on a hypergeometric test. At the same time, this study explored the relationship between NSAIDs and Alzheimer''s Disease. A total of 3,577 proteins in humans were identified to interact with NSAIDs from ChemDIS. Common proteins, functions and pathways affected by NSAIDs were analyzed from ChemDIS. The top disease categories associated with NSAIDs were cardiovascular system disease and disease of metabolism, followed by renal function disease. NSAIDs affecting Metabolism of lipids and lipoproteins, Arachidonic acid metabolism, Steroid hormone biosynthesis and other related action pathway is relation with these diseases.
The off-target effects of NSAIDs were systematically analyzed by computational methods. The association between NSAIDs and identified Alzheimer''s disease was consistent with literature. Indomethacin, Ibuprofen, Naproxen, Flurbiprofen, Aspirin, Sulindac may have beneficial effect on Alzheimer''s disease. Individual effects of these NSAIDs can be further investigated by integrating SNPs information

Identiferoai:union.ndltd.org:TW/104KMC05551019
Date January 2016
CreatorsYi-Hsuan Kuo, 郭伊玹
ContributorsChun-Wei Tung, 童俊維
Source SetsNational Digital Library of Theses and Dissertations in Taiwan
Languagezh-TW
Detected LanguageEnglish
Type學位論文 ; thesis
Format73

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