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Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
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Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
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ADAM17 and its proteolytic targets in disease pathogenesis.

Abdulbasit Amin1,2, Marina Badenes3,4,5

  • 1Gulbenkian Institute for Molecular Medicine (GIMM), Lisbon, Portugal.

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ADAM17, a protease regulating growth and inflammation, is a key target for treating cancer and inflammatory diseases. Its role extends to cardiovascular and metabolic conditions, highlighting its broad therapeutic potential.

Keywords:
ADAM17cancercardiovascular diseasesinflammationmetabolic diseases

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Pathophysiology

Background:

  • ADAM17, also known as TACE, is a metalloproteinase with over 90 substrates.
  • It regulates critical signaling pathways, including EGFR and TNF, impacting cell growth and inflammation.
  • ADAM17 is implicated in various diseases, making it a significant therapeutic target.

Purpose of the Study:

  • To review the current understanding of ADAM17.
  • To summarize the involvement of ADAM17 targets in major disease categories.
  • To highlight ADAM17's role in inflammation, cancer, and cardiovascular/metabolic diseases.

Main Methods:

  • Literature review of scientific publications.
  • Analysis of ADAM17's enzymatic activity and substrate interactions.
  • Synthesis of data on ADAM17's role in disease pathogenesis.

Main Results:

  • ADAM17 is a pleiotropic protease crucial for EGFR and TNF signaling.
  • Its substrates are involved in fundamental biological processes like growth and inflammation.
  • ADAM17 dysregulation is linked to cancer, inflammatory, cardiovascular, and metabolic diseases.

Conclusions:

  • ADAM17 is a central regulator in multiple signaling networks.
  • Targeting ADAM17 offers therapeutic potential for diverse pathological conditions.
  • Further research into ADAM17 biology can uncover novel treatment strategies.