Overexpression of endophilin A1 exacerbates synaptic alterations in a mouse model of Alzheimer’s disease
MetadataShow full item record
Altmetrics Handle Statistics
Altmetrics DOI Statistics
Endophilin A1 (EP) is a protein enriched in synaptic terminals that has been linked to Alzheimer’s disease (AD). Previous in vitro studies have shown that EP can bind to a variety of proteins, which elicit changes in synaptic transmission of neurotransmitters and spine formation. Additionally, we previously showed that EP protein levels are elevated in AD patients and AD transgenic animal models. Here, we establish the in vivo consequences of upregulation of EP expression in amyloid-β peptide (Aβ)-rich environments, leading to changes in both long-term potentiation and learning and memory of transgenic animals. Specifically, increasing EP augmented cerebral Aβ accumulation. EP-mediated signal transduction via reactive oxygen species (ROS)/p38 mitogen-activated protein (MAP) kinase contributes to Aβ-induced mitochondrial dysfunction, synaptic injury, and cognitive decline, which could be rescued by blocking either ROS or p38 MAP kinase activity.
Yu , Q , Wang , Y , Yan , S , Origlia , N , Rutigliano , G , Yu , H , Ainge , J A , Yan , S F , Gunn-Moore , F & Yan , S S 2018 , ' Overexpression of endophilin A1 exacerbates synaptic alterations in a mouse model of Alzheimer’s disease ' , Nature Communications , vol. 9 , 2968 . https://doi.org/10.1038/s41467-018-04389-0
© 2018 The Author(s). Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
DescriptionThis study was supported by grants from National Institute of Health Aging (NIA) and National Institute of Neurological Disorders and Stroke (NINDS) . F.G.-M. and J.A. were supported by the Alzheimer’s Research UK, the RS MacDonald Charitable Trust, and the BRAINS 600th Anniversary fund S.S.Y received Howard Mossberg Distinguished Professorship endowment from the University of Kansas.
Items in the St Andrews Research Repository are protected by copyright, with all rights reserved, unless otherwise indicated.