Abstract
While it is highly accepted that ADAM family members with ubiquitous expression patterns, such as ADAM10 and ADAM17 have major roles in homoeostasis and pathology, ADAM8 was initially considered as an immune-specific ADAM with a cell-specific expression pattern. Therefore, ADAM8 had a “sleeping beauty” existence for many years, and has recently come back into focus as it was detected under several pathological conditions. These were found to typically involve inflammation and remodelling of the extracellular matrix, including cancers and serious respiratory diseases such as asthma. In these diseases, induced expression of ADAM8 by different stimuli results in cleavage of various substrates, including cell adhesion molecules, cytokine receptors, and ECM components. Involvement of ADAM8 in individual diseases indicates its usefulness as both a diagnostic and prognostic marker. Even more strikingly, as ADAM8 progressively emerges as a key effector in pathological processes, so does its attractiveness as a therapeutic target rather than being a mere indicator of disease and its progression. This is encouraged by analysis of ADAM8 null mice, identifying no adverse phenotype in the absence of functional ADAM8. Thus, ADAM8 potentially is an attractive drug target in a variety of diseases. In this review, the current knowledge on ADAM8 in diseases and avenues for specific inhibition based on unique biochemical features of ADAM8 will be presented.
Keywords: ADAM8, Autocatalysis, Cell adhesion, Cancer invasion, Asthma, Neurodegeneration, Inflammation, Immunoevasion
Current Pharmaceutical Design
Title: ADAM8/MS2/CD156, an Emerging Drug Target in the Treatment of Inflammatory and Invasive Pathologies
Volume: 15 Issue: 20
Author(s): Garrit Koller, Uwe Schlomann, Panagiota Golfi, Taheera Ferdous, Silvia Naus and Jorg W. Bartsch
Affiliation:
Keywords: ADAM8, Autocatalysis, Cell adhesion, Cancer invasion, Asthma, Neurodegeneration, Inflammation, Immunoevasion
Abstract: While it is highly accepted that ADAM family members with ubiquitous expression patterns, such as ADAM10 and ADAM17 have major roles in homoeostasis and pathology, ADAM8 was initially considered as an immune-specific ADAM with a cell-specific expression pattern. Therefore, ADAM8 had a “sleeping beauty” existence for many years, and has recently come back into focus as it was detected under several pathological conditions. These were found to typically involve inflammation and remodelling of the extracellular matrix, including cancers and serious respiratory diseases such as asthma. In these diseases, induced expression of ADAM8 by different stimuli results in cleavage of various substrates, including cell adhesion molecules, cytokine receptors, and ECM components. Involvement of ADAM8 in individual diseases indicates its usefulness as both a diagnostic and prognostic marker. Even more strikingly, as ADAM8 progressively emerges as a key effector in pathological processes, so does its attractiveness as a therapeutic target rather than being a mere indicator of disease and its progression. This is encouraged by analysis of ADAM8 null mice, identifying no adverse phenotype in the absence of functional ADAM8. Thus, ADAM8 potentially is an attractive drug target in a variety of diseases. In this review, the current knowledge on ADAM8 in diseases and avenues for specific inhibition based on unique biochemical features of ADAM8 will be presented.
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Cite this article as:
Koller Garrit, Schlomann Uwe, Golfi Panagiota, Ferdous Taheera, Naus Silvia and Bartsch W. Jorg, ADAM8/MS2/CD156, an Emerging Drug Target in the Treatment of Inflammatory and Invasive Pathologies, Current Pharmaceutical Design 2009; 15 (20) . https://dx.doi.org/10.2174/138161209788682361
DOI https://dx.doi.org/10.2174/138161209788682361 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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