ADAM17 as a therapeutic target in multiple diseases
Joaquín Arribas1, Cary Esselens
1Institució Catalana de Recerca i Estudis Avançats (ICREA), Spain. jarribas@ir.vhebron.net
Current Pharmaceutical Design
|July 16, 2009
Summary
A Disintegrin and A Metalloproteinase 17 (ADAM17) is crucial for releasing membrane proteins, impacting diseases like cancer and inflammation. Overcoming therapeutic challenges is key to harnessing ADAM17
Area of Science:
- Biochemistry and Molecular Biology
- Cell Biology
- Pathology
Background:
- A Disintegrin and A Metalloproteinase 17 (ADAM17), also known as Tumor necrosis factor-alpha Converting Enzyme (TACE), is a key metalloproteinase.
- ADAM17 releases membrane-tethered proteins, influencing major pathologies including cancer, inflammation, and vascular diseases.
- Its broad substrate specificity allows it to activate growth factors, inactivate receptors, and cleave cell adhesion molecules.
Purpose of the Study:
- To review the multifaceted role of ADAM17 in both physiological processes and disease states.
- To highlight the therapeutic potential of targeting ADAM17.
- To identify challenges hindering the development of ADAM17 as a viable therapeutic target.
Main Methods:
- Literature review of existing research on ADAM17 function and substrates.
- Analysis of ADAM17's involvement in various disease pathologies.
- Discussion of proteolytic events, including Regulated Intramembrane Proteolysis (RIP) cascades.
Main Results:
- ADAM17 plays a critical role in shedding extracellular domains of growth factors and receptors, modulating cell signaling.
- Cleavage of cell adhesion molecules by ADAM17 impacts cell detachment and tissue remodeling.
- ADAM17 is implicated in diverse cellular processes and disease pathogenesis due to its wide range of substrates.
Conclusions:
- ADAM17 is a central regulator of cellular processes and a significant contributor to various diseases.
- Its role in activating growth factors and modulating cell adhesion makes it a promising therapeutic target.
- Further research is needed to address the challenges in developing effective and safe ADAM17-targeted therapies.
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