Title: An Overview of Notch Signaling in Adult Tissue Renewal and Maintenance
Volume: 9
Issue: 2
Author(s): Chihiro Sato, Guojun Zhao and Ma. Xenia G. Ilagan
Affiliation:
Keywords:
ADAM, CADASIL, -secretase, multiple sclerosis, Notch, T-ALL, stem cell, tissue renewal
Abstract: The Notch pathway is a critical mediator of short-range cell-cell communication that is reiteratively used to regulate a diverse array of cellular processes during embryonic development and the renewal and maintenance of adult tissues. Most Notch-dependent processes utilize a core signaling mechanism that is dependent on regulated intramembrane proteolysis: Upon ligand binding, Notch receptors undergo ectodomain shedding by ADAM metalloproteases, followed by γ-secretase-mediated intramembrane proteolysis. This releases the Notch intracellular domain, which translocates to the nucleus to activate transcription. In this review, we highlight the roles of Notch signaling particularly in self-renewing tissues in adults and several human diseases and raise some key considerations when targeting ADAMs and γ-secretase as disease-modifying strategies for Alzheimers Disease.
