title: Activation of NMDA receptors upregulates a disintegrin and metalloproteinase 10 via a Wnt/MAPK signaling pathway.
abstract: A disintegrin and metalloproteinase 10 (ADAM10) is the constitutive α-secretase that governs the nonamyloidogenic pathway of β-amyloid precursor protein processing and is an attractive drug target for treating Alzheimer's disease. To date, little is known about the mechanism by which ADAM10 is regulated in neurons. Using mouse primary cortical neurons, we show here that NMDA receptor (NMDAR) activation led to upregulation of the genes encoding ADAM10 and β-catenin proteins. Interestingly, the ADAM10 upregulation was abolished by inhibitors of Wnt/β-catenin signaling. Conversely, activation of the Wnt/β-catenin signaling pathway by recombinant Wnt3a stimulated ADAM10 expression. We further showed that both the NMDAR- and Wnt3a-induced ADAM10 upregulation was blocked by ERK inhibitors. We suggest that the NMDARs control ADAM10 expression via a Wnt/MAPK signaling pathway.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, Peoples Republic of China.
authors.forename: Xian-Zi
authors.initials: XZ
authors.lastname: Wan
authors.forename: Bei
authors.initials: B
authors.lastname: Li
authors.forename: Yi-Chen
authors.initials: YC
authors.lastname: Li
authors.forename: Xiang-Ling
authors.initials: XL
authors.lastname: Yang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Ling
authors.initials: L
authors.lastname: Zhong
authors.forename: Shao-Jun
authors.initials: SJ
authors.lastname: Tang
mesh_terms: D051722:ADAM Proteins / Q000096:biosynthesis*; D000072197:ADAM10 Protein; D053829:Amyloid Precursor Protein Secretases / Q000096:biosynthesis*; D000818:Animals; D002478:Cells, Cultured; D019483:Disintegrins / Q000096:biosynthesis; D005260:Female; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology*; D060449:Wnt Signaling Pathway / Q000502:physiology*; D060509:Wnt3A Protein / Q000096:biosynthesis*; D051176:beta Catenin / Q000096:biosynthesis
chemical_list: C495267:CTNNB1 protein, mouse; D019483:Disintegrins; D008565:Membrane Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse; D051176:beta Catenin; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491234:Adam10 protein, mouse