ADAM17 and its proteolytic targets in disease pathogenesis

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.