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New possibilities for manipulating Notch signalling
The Notch pathway is responsible for the correct development of many tissues and cell types. Recent findings link mutations and/or abnormal signalling of Notch receptors with the onset of human diseases. Therefore, the Notch pathway is a promising therapeutic target. Unfortunately, until recently, there have been no specific inhibitors and/or agonists for human Notch receptors (NOTCH1-4), 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 Notch-3 receptors. The most potent antibodies were found to bind to overlapping epitopes within a regulatory region that usually protects the Notch-3 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 antibodies-online.com:
Source:
Kang Li et al.: Modulation of Notch Signaling by Antibodies Specific for the Extracellular Negative Regulatory Region of NOTCH3, The Journal of Biological Chemistry 283, 8046-8054 (21st March 2008)
Michael S. Wolfe et al.: γ-Secretase Inhibition and Modulation for Alzheimer's Disease, Current Alzheimer Research 5, 158-164 (April 2008)
Kang Li et al.: Modulation of Notch Signaling by Antibodies Specific for the Extracellular Negative Regulatory Region of NOTCH3, The Journal of Biological Chemistry 283, 8046-8054 (21st March 2008)
Michael S. Wolfe et al.: γ-Secretase Inhibition and Modulation for Alzheimer's Disease, Current Alzheimer Research 5, 158-164 (April 2008)
17.07.2008 | Anna Lena Marwedel 
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