Regulation of NMDA receptor trafficking by amyloid-β
(2005) In Nature Neuroscience 8(8). p.1051-1058- Abstract
Amyloid-β peptide is elevated in the brains of patients with Alzheimer disease and is believed to be causative in the disease process. Amyloid-β reduces glutamatergic transmission and inhibits synaptic plasticity, although the underlying mechanisms are unknown. We found that application of amyloid-β 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-β by treating neurons with a γ-secretase inhibitor restored surface expression of NMDA receptors. Consistent with these data, amyloid-β application produced a rapid and persistent depression of NMDA-evoked currents in cortical neurons.... (More)
Amyloid-β peptide is elevated in the brains of patients with Alzheimer disease and is believed to be causative in the disease process. Amyloid-β reduces glutamatergic transmission and inhibits synaptic plasticity, although the underlying mechanisms are unknown. We found that application of amyloid-β 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-β by treating neurons with a γ-secretase inhibitor restored surface expression of NMDA receptors. Consistent with these data, amyloid-β application produced a rapid and persistent depression of NMDA-evoked currents in cortical neurons. Amyloid-β-dependent endocytosis of NMDA receptors required the α-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-β can cause synaptic dysfunction and contribute to Alzheimer disease pathology.
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- author
- publishing date
- 2005-08-01
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Nature Neuroscience
- volume
- 8
- issue
- 8
- pages
- 1051 - 1058
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:23044445669
- pmid:16025111
- ISSN
- 1097-6256
- DOI
- 10.1038/nn1503
- language
- English
- LU publication?
- no
- id
- e75d1c4a-1e2f-44df-9e8b-46c8aefb5cb1
- date added to LUP
- 2020-02-20 14:22:58
- date last changed
- 2024-09-05 16:55:03
@article{e75d1c4a-1e2f-44df-9e8b-46c8aefb5cb1, abstract = {{<p>Amyloid-β peptide is elevated in the brains of patients with Alzheimer disease and is believed to be causative in the disease process. Amyloid-β reduces glutamatergic transmission and inhibits synaptic plasticity, although the underlying mechanisms are unknown. We found that application of amyloid-β 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-β by treating neurons with a γ-secretase inhibitor restored surface expression of NMDA receptors. Consistent with these data, amyloid-β application produced a rapid and persistent depression of NMDA-evoked currents in cortical neurons. Amyloid-β-dependent endocytosis of NMDA receptors required the α-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-β can cause synaptic dysfunction and contribute to Alzheimer disease pathology.</p>}}, author = {{Snyder, Eric M. and Nong, Yi and Almeida, Claudia G. and Paul, Surojit and Moran, Timothy and Choi, Eun Young and Nairn, Angus C. and Salter, Michael W. and Lombroso, Paul J. and Gouras, Gunnar K. and Greengard, Paul}}, issn = {{1097-6256}}, language = {{eng}}, month = {{08}}, number = {{8}}, pages = {{1051--1058}}, publisher = {{Nature Publishing Group}}, series = {{Nature Neuroscience}}, title = {{Regulation of NMDA receptor trafficking by amyloid-β}}, url = {{http://dx.doi.org/10.1038/nn1503}}, doi = {{10.1038/nn1503}}, volume = {{8}}, year = {{2005}}, }