Cargando…
Oxidation of KCNB1 channels in the human brain and in mouse model of Alzheimer’s disease
Oxidative modification of the voltage-gated K(+) channel subfamily B member 1 (KCNB1, Kv2.1) is emerging as a mechanism of neuronal vulnerability potentially capable of affecting multiple conditions associated with oxidative stress, from normal aging to neurodegenerative disease. In this study we re...
Autores principales: | , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6062629/ https://www.ncbi.nlm.nih.gov/pubmed/30050035 http://dx.doi.org/10.1038/s41419-018-0886-1 |
_version_ | 1783342411151310848 |
---|---|
author | Wei, Yu Shin, Mi Ryung Sesti, Federico |
author_facet | Wei, Yu Shin, Mi Ryung Sesti, Federico |
author_sort | Wei, Yu |
collection | PubMed |
description | Oxidative modification of the voltage-gated K(+) channel subfamily B member 1 (KCNB1, Kv2.1) is emerging as a mechanism of neuronal vulnerability potentially capable of affecting multiple conditions associated with oxidative stress, from normal aging to neurodegenerative disease. In this study we report that oxidation of KCNB1 channels is exacerbated in the post mortem brains of Alzheimer’s disease (AD) donors compared to age-matched controls. In addition, phosphorylation of Focal Adhesion kinases (FAK) and Src tyrosine kinases, two key signaling steps that follow KCNB1 oxidation, is also strengthened in AD vs. control brains. Quadruple transgenic mice expressing a non-oxidizable form of KCNB1 in the 3xTg-AD background (APP(SWE), PS1(M146V), and tau(P301L)), exhibit improved working memory along with reduced brain inflammation, protein carbonylation and intraneuronal β-amyloid (Aβ) compared to 3xTg-AD mice or mice expressing the wild type (WT) KCNB1 channel. We conclude that oxidation of KCNB1 channels is a mechanism of neuronal vulnerability that is pervasive in the vertebrate brain. |
format | Online Article Text |
id | pubmed-6062629 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-60626292018-07-27 Oxidation of KCNB1 channels in the human brain and in mouse model of Alzheimer’s disease Wei, Yu Shin, Mi Ryung Sesti, Federico Cell Death Dis Article Oxidative modification of the voltage-gated K(+) channel subfamily B member 1 (KCNB1, Kv2.1) is emerging as a mechanism of neuronal vulnerability potentially capable of affecting multiple conditions associated with oxidative stress, from normal aging to neurodegenerative disease. In this study we report that oxidation of KCNB1 channels is exacerbated in the post mortem brains of Alzheimer’s disease (AD) donors compared to age-matched controls. In addition, phosphorylation of Focal Adhesion kinases (FAK) and Src tyrosine kinases, two key signaling steps that follow KCNB1 oxidation, is also strengthened in AD vs. control brains. Quadruple transgenic mice expressing a non-oxidizable form of KCNB1 in the 3xTg-AD background (APP(SWE), PS1(M146V), and tau(P301L)), exhibit improved working memory along with reduced brain inflammation, protein carbonylation and intraneuronal β-amyloid (Aβ) compared to 3xTg-AD mice or mice expressing the wild type (WT) KCNB1 channel. We conclude that oxidation of KCNB1 channels is a mechanism of neuronal vulnerability that is pervasive in the vertebrate brain. Nature Publishing Group UK 2018-07-26 /pmc/articles/PMC6062629/ /pubmed/30050035 http://dx.doi.org/10.1038/s41419-018-0886-1 Text en © The Author(s) 2018 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/. |
spellingShingle | Article Wei, Yu Shin, Mi Ryung Sesti, Federico Oxidation of KCNB1 channels in the human brain and in mouse model of Alzheimer’s disease |
title | Oxidation of KCNB1 channels in the human brain and in mouse model of Alzheimer’s disease |
title_full | Oxidation of KCNB1 channels in the human brain and in mouse model of Alzheimer’s disease |
title_fullStr | Oxidation of KCNB1 channels in the human brain and in mouse model of Alzheimer’s disease |
title_full_unstemmed | Oxidation of KCNB1 channels in the human brain and in mouse model of Alzheimer’s disease |
title_short | Oxidation of KCNB1 channels in the human brain and in mouse model of Alzheimer’s disease |
title_sort | oxidation of kcnb1 channels in the human brain and in mouse model of alzheimer’s disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6062629/ https://www.ncbi.nlm.nih.gov/pubmed/30050035 http://dx.doi.org/10.1038/s41419-018-0886-1 |
work_keys_str_mv | AT weiyu oxidationofkcnb1channelsinthehumanbrainandinmousemodelofalzheimersdisease AT shinmiryung oxidationofkcnb1channelsinthehumanbrainandinmousemodelofalzheimersdisease AT sestifederico oxidationofkcnb1channelsinthehumanbrainandinmousemodelofalzheimersdisease |