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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
PubMed

Insights

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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