Activation of NMDA receptors upregulates a disintegrin and metalloproteinase 10 via a Wnt/MAPK signaling pathway

Xian Zi Wan, Bei Li, Yi Chen Li, Xiang Ling Yang, Wei Zhang, Ling Zhong, Shao Jun Tang

Research output: Contribution to journalArticle

44 Scopus citations

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 encodingADAM10and β -catenin proteins. Interestingly, theADAM10upregulation 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.

Original languageEnglish (US)
Pages (from-to)3910-3916
Number of pages7
JournalJournal of Neuroscience
Volume32
Issue number11
DOIs
StatePublished - Mar 14 2012

ASJC Scopus subject areas

  • Neuroscience(all)

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