In:
eLife, eLife Sciences Publications, Ltd, Vol. 5 ( 2016-01-23)
Abstract:
Several neurodegenerative disorders, including Alzheimer’s disease, arise when protein-cutting enzymes process proteins in the wrong way. The resulting protein fragments can accumulate in nerve cells and cause them to die, leading to symptoms such as memory loss. In the case of Alzheimer’s disease the toxic protein fragment – called amyloid beta – can be produced when one enzyme cuts the amyloid precursor protein. However, the amyloid beta fragment is not made when a different enzyme called ADAM10 cuts the amyloid precursor protein first. There has been a lot of interest in finding drugs that activate ADAM10 to treat Alzheimer’s disease. However, ADAM10 also cuts other proteins on the surface of cells and it is important to know about these proteins if ADAM10 is going to be successfully targeted by a drug. To tackle this issue, Kuhn et al. have now searched for new proteins (or ‘substrates’) that are cut by ADAM10 in mouse nerve cells. The experiments identified proteins that were cut in normal nerve cells, but remained unprocessed in cells where the gene for ADAM10 had been deleted. This search uncovered almost 100 new substrates of ADAM10 that were then validated using biochemical techniques. Among these substrates were many proteins that are normally anchored into the membranes of nerve cells and involved in guiding and positioning these cells in the brain so that they can connect and communicate with each other. Kuhn et al. then deleted the gene for ADAM10 only in the frontmost part of the mouse brain. This led to the nerve cells forming abnormal networks in the regions of the brain that process smells and emotions. Overall the experiments proved that ADAM10 is important not only for the prevention of Alzheimer’s disease, but also for the normal development of the brain. Future studies could now explore how stimulating ADAM10 affects the levels of its substrates. Also, a better understanding of the substrates of ADAM10 may be useful both to predict side effects of drugs that activate ADAM10 and to monitor patients who are responding well to these drugs.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.12748.001
DOI:
10.7554/eLife.12748.002
DOI:
10.7554/eLife.12748.003
DOI:
10.7554/eLife.12748.004
DOI:
10.7554/eLife.12748.005
DOI:
10.7554/eLife.12748.006
DOI:
10.7554/eLife.12748.007
DOI:
10.7554/eLife.12748.008
DOI:
10.7554/eLife.12748.009
DOI:
10.7554/eLife.12748.010
DOI:
10.7554/eLife.12748.011
DOI:
10.7554/eLife.12748.012
DOI:
10.7554/eLife.12748.013
DOI:
10.7554/eLife.12748.014
DOI:
10.7554/eLife.12748.015
DOI:
10.7554/eLife.12748.016
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2016
detail.hit.zdb_id:
2687154-3
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