Potent and Selective inhibition of Acid Sphingomyelinase by Bisphosphonates
摘要:
The acid sphingomyelinase (aSMase) is emerging as an important drug target for a variety of diseases. Inhibition of aSMase prevents bacterial infections in a rat model of cystic fibrosis and formation of acute lung injury (ALI) elicited by endotoxin, acid instillation, or platelet-activating factor (PAF). Moreover, aSMase is essential for infection of non-phagocytotic cells with Neisseria gonorrhoeae and formation of pulmonary emphysema. Pharmacological or genetic inhibition of aSMase prevents apoptosis and degeneration of liver cells in a mouse model for Wilson's disease. In addition, there are several reports that aSMase significantly contributes to the formation of atherosclerotic plugs.
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年份:
2009
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