| First Author | Snyder EM | Year | 2005 |
| Journal | Nat Neurosci | Volume | 8 |
| Issue | 8 | Pages | 1051-8 |
| PubMed ID | 16025111 | Mgi Jnum | J:101438 |
| Mgi Id | MGI:3604036 | Doi | 10.1038/nn1503 |
| Citation | Snyder EM, et al. (2005) Regulation of NMDA receptor trafficking by amyloid-beta. Nat Neurosci 8(8):1051-8 |
| abstractText | Amyloid-beta peptide is elevated in the brains of patients with Alzheimer disease and is believed to be causative in the disease process. Amyloid-beta reduces glutamatergic transmission and inhibits synaptic plasticity, although the underlying mechanisms are unknown. We found that application of amyloid-beta promoted endocytosis of NMDA receptors in cortical neurons. In addition, neurons from a genetic mouse model of Alzheimer disease expressed reduced amounts of surface NMDA receptors. Reducing amyloid-beta by treating neurons with a gamma-secretase inhibitor restored surface expression of NMDA receptors. Consistent with these data, amyloid-beta application produced a rapid and persistent depression of NMDA-evoked currents in cortical neurons. Amyloid-beta-dependent endocytosis of NMDA receptors required the alpha-7 nicotinic receptor, protein phosphatase 2B (PP2B) and the tyrosine phosphatase STEP. Dephosphorylation of the NMDA receptor subunit NR2B at Tyr1472 correlated with receptor endocytosis. These data indicate a new mechanism by which amyloid-beta can cause synaptic dysfunction and contribute to Alzheimer disease pathology. |
