New possibilities for manipulating Notch signalling

The is responsible for the correct development of many tissues and cell types. Recent findings link mutations and/or abnormal signalling of with the onset of human diseases. Therefore, the is a promising therapeutic target. Unfortunately, until recently, there have been no specific inhibitors and/or agonists for human Notch receptors (), leaving the potential unexplored.

Recent reports and progress:

1. In vivo toxicity of an amyloid beta peptide inhibitor in clinical trials was linked to blockade of the receptor Notch. The inhibitor was originally directed against the amyloid beta peptide due to its role in the pathogenesis of Alzheimer's disease. Notch signalling is suppressed, however the drug could not be developed as treatment option for Alzheimer's disease. On the other hand, though, it offers great opportunities in the treatment of Notch-related diseases like diabetes, inflammatory kidney disease and cancer.

2. Another approach has been taken to develop monoclonal antibodies that specifically bind receptors. The most potent antibodies were found to bind to overlapping epitopes within a regulatory region that usually protects the extracellular domain from proteolysis, when it is auto-activated. By means of these antibodies, as well as modulators of γ-secretase activities, a wide range of tools to manipulate Notch signalling might soon be available and hold the promise as novel therapeutic interventions.

Related antibodies on

Notch 1 (cleaved N-terminus)

Amyloid-β protein