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dc.contributor.authorZhang, Hongju
dc.contributor.authorWang, Yongfu
dc.contributor.authorYan, Shijun
dc.contributor.authorDu, Fang
dc.contributor.authorWu, Long
dc.contributor.authorYan, Shiqiang
dc.contributor.authorYan, Shirley ShiDu
dc.date.accessioned2016-02-12T21:42:42Z
dc.date.available2016-02-12T21:42:42Z
dc.date.issued2014-06-12
dc.identifier.citationZhang, Hongju, Yongfu Wang, Shijun Yan, Fang Du, Long Wu, Shiqiang Yan, and Shirley S. Yan. "Genetic Deficiency of Neuronal RAGE Protects against AGE-induced Synaptic Injury." Cell Death Dis Cell Death and Disease 5.6 (2014): n. pag. doi:10.1038/cddis.2014.248.en_US
dc.identifier.urihttp://hdl.handle.net/1808/20069
dc.description.abstractSynaptic dysfunction and degeneration is an early pathological feature of aging and age-related diseases, including Alzheimer's disease (AD). Aging is associated with increased generation and deposition of advanced glycation endproducts (AGEs), resulting from nonenzymatic glycation (or oxidation) proteins and lipids. AGE formation is accelerated in diabetes and AD-affected brain, contributing to cellular perturbation. The extent of AGEs' involvement, if at all, in alterations in synaptic structure and function is currently unknown. Here we analyze the contribution of neuronal receptor of AGEs (RAGE) signaling to AGE-mediated synaptic injury using novel transgenic neuronal RAGE knockout mice specifically targeted to the forebrain and transgenic mice expressing neuronal dominant-negative RAGE (DN-RAGE). Addition of AGEs to brain slices impaired hippocampal long-term potentiation (LTP). Similarly, treatment of hippocampal neurons with AGEs significantly decreases synaptic density. Such detrimental effects are largely reversed by genetic RAGE depletion. Notably, brain slices from mice with neuronal RAGE deficiency or DN-RAGE are resistant to AGE-induced LTP deficit. Further, RAGE deficiency or DN-RAGE blocks AGE-induced activation of p38 signaling. Taken together, these data show that neuronal RAGE functions as a signal transducer for AGE-induced synaptic dysfunction, thereby providing new insights into a mechanism by which the AGEs–RAGE-dependent signaling cascade contributes to synaptic injury via the p38 MAP kinase signal transduction pathway. Thus, RAGE blockade may be a target for development of interventions aimed at preventing the progression of cognitive decline in aging and age-related neurodegenerative diseases.en_US
dc.publisherNature Publishing Groupen_US
dc.rightsCell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/
dc.titleGenetic deficiency of neuronal RAGE protects against AGE-induced synaptic injuryen_US
dc.typeArticle
kusw.kuauthorYan, Shijun
kusw.kudepartmentHiguchi Biosciences Centeren_US
dc.identifier.doi10.1038/cddis.2014.248
dc.identifier.orcidhttps://orcid.org/0000-0003-3499-0586 https://orcid.org/0000-0003-1165-1784
kusw.oaversionScholarly/refereed, publisher version
kusw.oapolicyThis item meets KU Open Access policy criteria.
dc.rights.accessrightsopenAccess


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Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
Except where otherwise noted, this item's license is described as: Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/