The shedding protease ADAM17: Physiology and pathophysiology

Area of Science:

• Biochemistry
• Molecular Biology
• Immunology

Background:

• ADAM17 (a disintegrin and metalloprotease) is a key enzyme involved in shedding cell surface proteins.
• Its roles in physiological processes and diseases are under extensive investigation.
• Understanding ADAM17's regulation and activity is critical for therapeutic targeting.

Purpose of the Study:

• To review the physiological functions of ADAM17 in health and disease.
• To discuss ADAM17's substrates, genetic models, and roles in immunity, cancer, and the central nervous system.
• To explore novel methods for studying ADAM17 in the brain.

Main Methods:

• Literature review of existing studies on ADAM17.
• Analysis of mouse models with ADAM17 deficiencies.
• Expression analysis of ADAM17 in human dopaminergic neurons derived from induced pluripotent stem cells.

Main Results:

• ADAM17 significantly impacts the immune system and cancer development through its regulation of EGF-R, IL-6, and TNFα.
• The precise function of ADAM17 in the central nervous system and neurodegeneration remains largely unknown.
• ADAM17 expression is confirmed in human dopaminergic neurons.

Conclusions:

• ADAM17 is a critical regulator in immunity and cancer, with established roles in EGF-R, IL-6, and TNFα pathways.
• Further research is needed to elucidate ADAM17's function in neurodegeneration.
• Induced pluripotent stem cell technology offers a promising avenue for studying ADAM17 in neural contexts.