PT  - JOURNAL ARTICLE
AU  - Xian-Zi Wan
AU  - Bei Li
AU  - Yi-Chen Li
AU  - Xiang-Ling Yang
AU  - Wei Zhang
AU  - Ling Zhong
AU  - Shao-Jun Tang
TI  - Activation of NMDA Receptors Upregulates A Disintegrin and Metalloproteinase 10 via a Wnt/MAPK Signaling Pathway
AID  - 10.1523/JNEUROSCI.3916-11.2012
DP  - 2012 Mar 14
TA  - The Journal of Neuroscience
PG  - 3910--3916
VI  - 32
IP  - 11
4099  - http://www.jneurosci.org/content/32/11/3910.short
4100  - http://www.jneurosci.org/content/32/11/3910.full
SO  - J. Neurosci.2012 Mar 14; 32
AB  - 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.