| First Author | Lourenço FC | Year | 2009 |
| Journal | Cell Death Differ | Volume | 16 |
| Issue | 5 | Pages | 655-63 |
| PubMed ID | 19148186 | Mgi Jnum | J:164195 |
| Mgi Id | MGI:4830861 | Doi | 10.1038/cdd.2008.191 |
| Citation | Lourenco FC, et al. (2009) Netrin-1 interacts with amyloid precursor protein and regulates amyloid-beta production. Cell Death Differ 16(5):655-63 |
| abstractText | The beta-amyloid precursor protein (APP) is an orphan transmembrane receptor whose physiological role is largely unknown. APP is cleaved by proteases generating amyloid-beta (Abeta) 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 Abeta peptide production in brain slices from Alzheimer model transgenic mice. In this mouse model, decreased netrin-1 expression is associated with increased Abeta concentration, thus supporting netrin-1 as a key regulator of Abeta 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. |
