Authors: Bhuiyan, Md. S.; Fukunaga, Kohji

Source: Current Drug Targets, Volume 10, Number 4, April 2009 , pp. 372-383(12)

Publisher: Bentham Science Publishers

Abstract:

Deregulation of apoptosis has been shown to contribute to the development of many diseases, including ischemia/ reperfusion injury of organs, different types of cancer formation, as well as neurodegenerative and autoimmune disorders. Recently, the mitochondrial serine protease High temperature requirement A2 (HtrA2)/Omi has drawn attention as it played pivotal role in different pathological conditions. We critically discussed the rationale for therapeutically targeting HtrA2 signaling in pathological conditions and explore the molecular mechanisms of HtrA2 inhibition as a novel therapeutic strategy. The precise mode of action and importance of HtrA2 in mitochondrial quality control as well as in apoptosis in mammalian cells has been recently studied through biochemical, structural and genetic studies. This review introduces HrtA2 from its molecular origins, discusses its modulation and potential as a novel drug target, and considers future therapeutic perspectives.

Keywords: HtrA2; apoptosis; mitochondria; inhibitor of apoptosis proteins; caspases

Document Type: Research article

Publication date: 2009-04-01

More about this publication?

• Current Drug Targets aims to cover the latest and most outstanding developments on the medicinal chemistry and pharmacology of molecular drug targets e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal will be devoted to a single timely topic, with series of in-depth reviews, written by leaders in the field, covering a range of current topics on drug targets. These issues will be organized and led by a guest editor who is a recognized expert in the overall topic. As the discovery, identification, characterisation and validation of novel human drug targets for drug discovery continues to grow; this journal will be essential reading for all pharmaceutical scientists involved in drug discovery and development.

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