Overexpression of endophilin A1 exacerbates synaptic alterations in a mouse model of Alzheimer’s disease

Qing Yu; Yongfu Wang; Shijun Yan; Nicola Origlia; Grazia Rutigliano; Haiyang Yu; James Alexander Ainge; Shi Fang Yan; Frank Gunn-Moore; Shirley ShiDu Yan

doi:10.1038/s41467-018-04389-0

Overexpression of endophilin A1 exacerbates synaptic alterations in a mouse model of Alzheimer’s disease

Qing Yu, Yongfu Wang, Shijun Yan, Nicola Origlia, Grazia Rutigliano, Haiyang Yu, James Alexander Ainge, Shi Fang Yan, Frank Gunn-Moore, Shirley ShiDu Yan

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Abstract

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.

Original language	English
Article number	2968
Number of pages	14
Journal	Nature Communications
Volume	9
DOIs	https://doi.org/10.1038/s41467-018-04389-0
Publication status	Published - 30 Jul 2018

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Yu_2018_NC_EndophilinA1_CC
© 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/.
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James Ainge
- jaa7st-andrews.acuk
- School of Psychology and Neuroscience - Head of the School of Psychology and Neuroscience, Professor
- Institute of Behavioural and Neural Sciences
Person: Academic
Frank J Gunn-Moore
- fjg1st-andrews.acuk
Person: Academic

Cite this

@article{205ebedd7f294774ba2858270f69760b,

title = "Overexpression of endophilin A1 exacerbates synaptic alterations in a mouse model of Alzheimer{\textquoteright}s disease",

abstract = "Endophilin A1 (EP) is a protein enriched in synaptic terminals that has been linked to Alzheimer{\textquoteright}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.",

author = "Qing Yu and Yongfu Wang and Shijun Yan and Nicola Origlia and Grazia Rutigliano and Haiyang Yu and Ainge, {James Alexander} and Yan, {Shi Fang} and Frank Gunn-Moore and Yan, {Shirley ShiDu}",

note = "This 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{\textquoteright}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.",

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T1 - Overexpression of endophilin A1 exacerbates synaptic alterations in a mouse model of Alzheimer’s disease

AU - Yu, Qing

AU - Wang, Yongfu

AU - Yan, Shijun

AU - Origlia, Nicola

AU - Rutigliano, Grazia

AU - Yu, Haiyang

AU - Ainge, James Alexander

AU - Yan, Shi Fang

AU - Gunn-Moore, Frank

AU - Yan, Shirley ShiDu

N1 - This 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.

PY - 2018/7/30

Y1 - 2018/7/30

N2 - 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.

AB - 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.

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M3 - Article

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VL - 9

JO - Nature Communications

JF - Nature Communications

M1 - 2968

ER -

Overexpression of endophilin A1 exacerbates synaptic alterations in a mouse model of Alzheimer’s disease

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James Ainge

Frank J Gunn-Moore

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