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Impact of RTN3 Deficiency on Expression of BACE1 and Amyloid Deposition
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Zeitschriftentitel: | The Journal of Neuroscience |
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Personen und Körperschaften: | , , , , , , , |
In: | The Journal of Neuroscience, 34, 2014, 42, S. 13954-13962 |
Format: | E-Article |
Sprache: | Englisch |
veröffentlicht: |
Society for Neuroscience
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Schlagwörter: |
author_facet |
Shi, Qi Ge, Yingying Sharoar, Md. Golam He, Wanxia Xiang, Rong Zhang, Zhuohua Hu, Xiangyou Yan, Riqiang Shi, Qi Ge, Yingying Sharoar, Md. Golam He, Wanxia Xiang, Rong Zhang, Zhuohua Hu, Xiangyou Yan, Riqiang |
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author |
Shi, Qi Ge, Yingying Sharoar, Md. Golam He, Wanxia Xiang, Rong Zhang, Zhuohua Hu, Xiangyou Yan, Riqiang |
spellingShingle |
Shi, Qi Ge, Yingying Sharoar, Md. Golam He, Wanxia Xiang, Rong Zhang, Zhuohua Hu, Xiangyou Yan, Riqiang The Journal of Neuroscience Impact of RTN3 Deficiency on Expression of BACE1 and Amyloid Deposition General Neuroscience |
author_sort |
shi, qi |
spelling |
Shi, Qi Ge, Yingying Sharoar, Md. Golam He, Wanxia Xiang, Rong Zhang, Zhuohua Hu, Xiangyou Yan, Riqiang 0270-6474 1529-2401 Society for Neuroscience General Neuroscience http://dx.doi.org/10.1523/jneurosci.1588-14.2014 <jats:p>Reticulon 3 (RTN3) has previously been shown to interact with BACE1 and negatively regulate BACE1 activity. To what extent RTN3 deficiency affects BACE1 activity is an intriguing question. In this study, we aimed to address this by generating RTN3-null mice. Mice with complete deficiency of RTN3 grow normally and have no obviously discernible phenotypes. Morphological analyses of RTN3-null mice showed no significant alterations in cellular structure, although RTN3 is recognized as a protein contributing to the shaping of tubular endoplasmic reticulum. Biochemical analysis revealed that RTN3 deficiency increased protein levels of BACE1. This elevation of BACE1 levels correlated with enhanced processing of amyloid precursor protein at the β-secretase site. We also demonstrated that RTN3 deficiency in Alzheimer's mouse models facilitates amyloid deposition, further supporting an<jats:italic>in vivo</jats:italic>role of RTN3 in the regulation of BACE1 activity. Since it has been shown that RTN3 monomer is reduced in brains of Alzheimer's patients, our results suggest that long-lasting reduction of RTN3 levels has adverse effects on BACE1 activity and may contribute to Alzheimer's pathogenesis.</jats:p> Impact of RTN3 Deficiency on Expression of BACE1 and Amyloid Deposition The Journal of Neuroscience |
doi_str_mv |
10.1523/jneurosci.1588-14.2014 |
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title |
Impact of RTN3 Deficiency on Expression of BACE1 and Amyloid Deposition |
title_unstemmed |
Impact of RTN3 Deficiency on Expression of BACE1 and Amyloid Deposition |
title_full |
Impact of RTN3 Deficiency on Expression of BACE1 and Amyloid Deposition |
title_fullStr |
Impact of RTN3 Deficiency on Expression of BACE1 and Amyloid Deposition |
title_full_unstemmed |
Impact of RTN3 Deficiency on Expression of BACE1 and Amyloid Deposition |
title_short |
Impact of RTN3 Deficiency on Expression of BACE1 and Amyloid Deposition |
title_sort |
impact of rtn3 deficiency on expression of bace1 and amyloid deposition |
topic |
General Neuroscience |
url |
http://dx.doi.org/10.1523/jneurosci.1588-14.2014 |
publishDate |
2014 |
physical |
13954-13962 |
description |
<jats:p>Reticulon 3 (RTN3) has previously been shown to interact with BACE1 and negatively regulate BACE1 activity. To what extent RTN3 deficiency affects BACE1 activity is an intriguing question. In this study, we aimed to address this by generating RTN3-null mice. Mice with complete deficiency of RTN3 grow normally and have no obviously discernible phenotypes. Morphological analyses of RTN3-null mice showed no significant alterations in cellular structure, although RTN3 is recognized as a protein contributing to the shaping of tubular endoplasmic reticulum. Biochemical analysis revealed that RTN3 deficiency increased protein levels of BACE1. This elevation of BACE1 levels correlated with enhanced processing of amyloid precursor protein at the β-secretase site. We also demonstrated that RTN3 deficiency in Alzheimer's mouse models facilitates amyloid deposition, further supporting an<jats:italic>in vivo</jats:italic>role of RTN3 in the regulation of BACE1 activity. Since it has been shown that RTN3 monomer is reduced in brains of Alzheimer's patients, our results suggest that long-lasting reduction of RTN3 levels has adverse effects on BACE1 activity and may contribute to Alzheimer's pathogenesis.</jats:p> |
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author | Shi, Qi, Ge, Yingying, Sharoar, Md. Golam, He, Wanxia, Xiang, Rong, Zhang, Zhuohua, Hu, Xiangyou, Yan, Riqiang |
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author_sort | shi, qi |
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description | <jats:p>Reticulon 3 (RTN3) has previously been shown to interact with BACE1 and negatively regulate BACE1 activity. To what extent RTN3 deficiency affects BACE1 activity is an intriguing question. In this study, we aimed to address this by generating RTN3-null mice. Mice with complete deficiency of RTN3 grow normally and have no obviously discernible phenotypes. Morphological analyses of RTN3-null mice showed no significant alterations in cellular structure, although RTN3 is recognized as a protein contributing to the shaping of tubular endoplasmic reticulum. Biochemical analysis revealed that RTN3 deficiency increased protein levels of BACE1. This elevation of BACE1 levels correlated with enhanced processing of amyloid precursor protein at the β-secretase site. We also demonstrated that RTN3 deficiency in Alzheimer's mouse models facilitates amyloid deposition, further supporting an<jats:italic>in vivo</jats:italic>role of RTN3 in the regulation of BACE1 activity. Since it has been shown that RTN3 monomer is reduced in brains of Alzheimer's patients, our results suggest that long-lasting reduction of RTN3 levels has adverse effects on BACE1 activity and may contribute to Alzheimer's pathogenesis.</jats:p> |
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spelling | Shi, Qi Ge, Yingying Sharoar, Md. Golam He, Wanxia Xiang, Rong Zhang, Zhuohua Hu, Xiangyou Yan, Riqiang 0270-6474 1529-2401 Society for Neuroscience General Neuroscience http://dx.doi.org/10.1523/jneurosci.1588-14.2014 <jats:p>Reticulon 3 (RTN3) has previously been shown to interact with BACE1 and negatively regulate BACE1 activity. To what extent RTN3 deficiency affects BACE1 activity is an intriguing question. In this study, we aimed to address this by generating RTN3-null mice. Mice with complete deficiency of RTN3 grow normally and have no obviously discernible phenotypes. Morphological analyses of RTN3-null mice showed no significant alterations in cellular structure, although RTN3 is recognized as a protein contributing to the shaping of tubular endoplasmic reticulum. Biochemical analysis revealed that RTN3 deficiency increased protein levels of BACE1. This elevation of BACE1 levels correlated with enhanced processing of amyloid precursor protein at the β-secretase site. We also demonstrated that RTN3 deficiency in Alzheimer's mouse models facilitates amyloid deposition, further supporting an<jats:italic>in vivo</jats:italic>role of RTN3 in the regulation of BACE1 activity. Since it has been shown that RTN3 monomer is reduced in brains of Alzheimer's patients, our results suggest that long-lasting reduction of RTN3 levels has adverse effects on BACE1 activity and may contribute to Alzheimer's pathogenesis.</jats:p> Impact of RTN3 Deficiency on Expression of BACE1 and Amyloid Deposition The Journal of Neuroscience |
spellingShingle | Shi, Qi, Ge, Yingying, Sharoar, Md. Golam, He, Wanxia, Xiang, Rong, Zhang, Zhuohua, Hu, Xiangyou, Yan, Riqiang, The Journal of Neuroscience, Impact of RTN3 Deficiency on Expression of BACE1 and Amyloid Deposition, General Neuroscience |
title | Impact of RTN3 Deficiency on Expression of BACE1 and Amyloid Deposition |
title_full | Impact of RTN3 Deficiency on Expression of BACE1 and Amyloid Deposition |
title_fullStr | Impact of RTN3 Deficiency on Expression of BACE1 and Amyloid Deposition |
title_full_unstemmed | Impact of RTN3 Deficiency on Expression of BACE1 and Amyloid Deposition |
title_short | Impact of RTN3 Deficiency on Expression of BACE1 and Amyloid Deposition |
title_sort | impact of rtn3 deficiency on expression of bace1 and amyloid deposition |
title_unstemmed | Impact of RTN3 Deficiency on Expression of BACE1 and Amyloid Deposition |
topic | General Neuroscience |
url | http://dx.doi.org/10.1523/jneurosci.1588-14.2014 |