科研之友
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摘要
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 gamma-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 gamma-secretase as disease-modifying strategies for Alzheimer's Disease.
- 出版日期2012-2
