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Netrin-1 interacts with amyloid precursor protein and regulates amyloid-β production
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Netrin-1 interacts with amyloid precursor protein and regulates amyloid-β production
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Journal Article
Netrin-1 interacts with amyloid precursor protein and regulates amyloid-β production
2009
Overview
The
β
-amyloid precursor protein (APP) is an orphan transmembrane receptor whose physiological role is largely unknown. APP is cleaved by proteases generating amyloid-
β
(A
β
) peptide, the main component of the amyloid plaques that are associated with Alzheimer's disease. Here, we show that APP binds netrin-1, a multifunctional guidance and trophic factor. Netrin-1 binding modulates APP signaling triggering APP intracellular domain (AICD)-dependent gene transcription. Furthermore, netrin-1 binding suppresses A
β
peptide production in brain slices from Alzheimer model transgenic mice. In this mouse model, decreased netrin-1 expression is associated with increased A
β
concentration, thus supporting netrin-1 as a key regulator of A
β
production. Finally, we show that netrin-1 brain administration in Alzheimer model transgenic mice may be associated with an amelioration of the Alzheimer's phenotype.
Publisher
Nature Publishing Group UK
Subject
Amyloid beta-Peptides - metabolism
/ Amyloid beta-Protein Precursor - metabolism
/ Animals
/ Biomedical and Life Sciences
/ Humans
/ Mice
/ Nerve Growth Factors - administration & dosage
/ Nerve Growth Factors - metabolism
/ Netrin-1
/ Recombinant Proteins - administration & dosage
/ Recombinant Proteins - metabolism
