ADAM10

ADAM10 (A Disintegrin And Metalloproteinase 10), also known as Kuzbanian homolog or CD156c, is a transmembrane zinc-dependent protease critical for regulated proteolysis of cell surface proteins. It mediates ectodomain shedding of substrates including Notch receptors, amyloid precursor protein (APP), and adhesion molecules, thereby modulating cell signaling, adhesion, and migration. ADAM10 is indispensable for Notch signaling activation during embryonic development and tissue homeostasis. Its sheddase activity also regulates growth factor release (e.g., EGFR ligands) and immune responses through cleavage of cytokines like TNF-α. Dysregulation of ADAM10 is implicated in Alzheimer’s disease (via altered APP processing leading to amyloid-β accumulation), cancer (enhanced EGFR signaling and epithelial-mesenchymal transition), and inflammatory disorders. Pharmacological targeting remains challenging due to substrate diversity; selective inhibitors (e.g., GI254023X) and monoclonal antibodies are under preclinical investigation for oncology, while ADAM10 activators are explored for neurodegenerative diseases. Balancing therapeutic efficacy with off-target effects on physiological substrates remains a key research focus.