RGD Reference Report - Reversing EphB2 depletion rescues cognitive functions in Alzheimer model. - Rat Genome Database

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Reversing EphB2 depletion rescues cognitive functions in Alzheimer model.

Authors: Cissé, Moustapha  Halabisky, Brian  Harris, Julie  Devidze, Nino  Dubal, Dena B  Sun, Binggui  Orr, Anna  Lotz, Gregor  Kim, Daniel H  Hamto, Patricia  Ho, Kaitlyn  Yu, Gui-Qiu  Mucke, Lennart 
Citation: Cissé M, etal., Nature. 2011 Jan 6;469(7328):47-52. doi: 10.1038/nature09635. Epub 2010 Nov 28.
RGD ID: 12859080
Pubmed: (View Article at PubMed) PMID:21113149
DOI: Full-text: DOI:10.1038/nature09635

Amyloid-ß oligomers may cause cognitive deficits in Alzheimer's disease by impairing neuronal NMDA-type glutamate receptors, whose function is regulated by the receptor tyrosine kinase EphB2. Here we show that amyloid-ß oligomers bind to the fibronectin repeats domain of EphB2 and trigger EphB2 degradation in the proteasome. To determine the pathogenic importance of EphB2 depletions in Alzheimer's disease and related models, we used lentiviral constructs to reduce or increase neuronal expression of EphB2 in memory centres of the mouse brain. In nontransgenic mice, knockdown of EphB2 mediated by short hairpin RNA reduced NMDA receptor currents and impaired long-term potentiation in the dentate gyrus, which are important for memory formation. Increasing EphB2 expression in the dentate gyrus of human amyloid precursor protein transgenic mice reversed deficits in NMDA receptor-dependent long-term potentiation and memory impairments. Thus, depletion of EphB2 is critical in amyloid-ß-induced neuronal dysfunction. Increasing EphB2 levels or function could be beneficial in Alzheimer's disease.

Annotation

Gene Ontology Annotations    

Biological Process

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Ephb2  (Eph receptor B2)

Objects referenced in this article
0 Efnb2 ephrin B2 All species

Additional Information