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.
Keywords: ADAM, CADASIL, -secretase, multiple sclerosis, Notch, T-ALL, stem cell, tissue renewal
Current Alzheimer Research
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.
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Cite this article as:
Sato Chihiro, Zhao Guojun and Xenia G. Ilagan Ma., An Overview of Notch Signaling in Adult Tissue Renewal and Maintenance, Current Alzheimer Research 2012; 9 (2) . https://dx.doi.org/10.2174/156720512799361600
DOI https://dx.doi.org/10.2174/156720512799361600 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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