ADAM17, shedding, TACE as therapeutic targets

作者：Rose John Stefan^*

来源：Pharmacological Research, 2013, 71: 19-22.

DOI：10.1016/j.phrs.2013.01.012

• ADAM proteases
• ADAM17
• TACE
• Shedding
• IL-6 trans-signaling
• TNF alpha

ADAM17 has been molecularly cloned as the enzyme responsible for cleavage of the transmembrane protein TNF alpha (TNF alpha converting enzyme, TACE). Later it was realized that ADAM17 was also responsible for the processing of cell adhesion proteins, cytokine and growth factor receptors and many ligands of the EGF receptor. Since TNF alpha is a target of anti-inflammatory therapies, it was speculated that inhibition of ADAM17 might be a therapeutic strategy in the treatment of inflammation or inflammation associated cancer. Meanwhile it has been recognized that ADAM17 governs many vital functions in the body and loss of ADAM17 leads to severe defects in the skin and to high susceptibility of the intestine to inflammation. Here I summarize data on the physiologic role of ADAM17 and the feasibility of specific blockade of this enzyme.

• 出版日期2013-5