c-Jun N-terminal Kinase (JNK) induces phosphorylation of amyloid precursor protein (APP) at Thr668, in okadaic acid-induced neurodegeneration

Several lines of evidence have revealed that phosphorylation of amyloid precursor protein (APP) at Thr668 is involved in the pathogenesis of Alzheimer’s disease (AD). Okadaic acid (OA), a protein phosphatase-2A inhibitor, has been used in AD research models to increase tau phosphorylation and induce...

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Autores principales: Ahn, Ji-Hwan, So, Sang-Pil, Kim, Na-Young, Kim, Hyun-Ju, Yoon, Seung-Yong, Kim, Dong-Hou
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Korean Society for Biochemistry and Molecular Biology 2016
Materias:
Research Articles
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5032005/
https://www.ncbi.nlm.nih.gov/pubmed/26839154
http://dx.doi.org/10.5483/BMBRep.2016.49.7.246
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author Ahn, Ji-Hwan
So, Sang-Pil
Kim, Na-Young
Kim, Hyun-Ju
Yoon, Seung-Yong
Kim, Dong-Hou
author_facet Ahn, Ji-Hwan
So, Sang-Pil
Kim, Na-Young
Kim, Hyun-Ju
Yoon, Seung-Yong
Kim, Dong-Hou
author_sort Ahn, Ji-Hwan
collection PubMed
description Several lines of evidence have revealed that phosphorylation of amyloid precursor protein (APP) at Thr668 is involved in the pathogenesis of Alzheimer’s disease (AD). Okadaic acid (OA), a protein phosphatase-2A inhibitor, has been used in AD research models to increase tau phosphorylation and induce neuronal death. We previously showed that OA increased levels of APP and induced accumulation of APP in axonal swellings. In this study, we found that in OA-treated neurons, phosphorylation of APP at Thr668 increased and accumulated in axonal swellings by c-jun N-terminal kinase (JNK), and not by Cdk5 or ERK/MAPK. These results suggest that JNK may be one of therapeutic targets for the treatment of AD. [BMB Reports 2016; 49(7): 376-381]
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spelling pubmed-50320052016-09-29 c-Jun N-terminal Kinase (JNK) induces phosphorylation of amyloid precursor protein (APP) at Thr668, in okadaic acid-induced neurodegeneration Ahn, Ji-Hwan So, Sang-Pil Kim, Na-Young Kim, Hyun-Ju Yoon, Seung-Yong Kim, Dong-Hou BMB Rep Research Articles Several lines of evidence have revealed that phosphorylation of amyloid precursor protein (APP) at Thr668 is involved in the pathogenesis of Alzheimer’s disease (AD). Okadaic acid (OA), a protein phosphatase-2A inhibitor, has been used in AD research models to increase tau phosphorylation and induce neuronal death. We previously showed that OA increased levels of APP and induced accumulation of APP in axonal swellings. In this study, we found that in OA-treated neurons, phosphorylation of APP at Thr668 increased and accumulated in axonal swellings by c-jun N-terminal kinase (JNK), and not by Cdk5 or ERK/MAPK. These results suggest that JNK may be one of therapeutic targets for the treatment of AD. [BMB Reports 2016; 49(7): 376-381] Korean Society for Biochemistry and Molecular Biology 2016-07-31 /pmc/articles/PMC5032005/ /pubmed/26839154 http://dx.doi.org/10.5483/BMBRep.2016.49.7.246 Text en Copyright © 2016, Korean Society for Biochemistry and Molecular Biology http://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Ahn, Ji-Hwan
So, Sang-Pil
Kim, Na-Young
Kim, Hyun-Ju
Yoon, Seung-Yong
Kim, Dong-Hou
c-Jun N-terminal Kinase (JNK) induces phosphorylation of amyloid precursor protein (APP) at Thr668, in okadaic acid-induced neurodegeneration
title c-Jun N-terminal Kinase (JNK) induces phosphorylation of amyloid precursor protein (APP) at Thr668, in okadaic acid-induced neurodegeneration
title_full c-Jun N-terminal Kinase (JNK) induces phosphorylation of amyloid precursor protein (APP) at Thr668, in okadaic acid-induced neurodegeneration
title_fullStr c-Jun N-terminal Kinase (JNK) induces phosphorylation of amyloid precursor protein (APP) at Thr668, in okadaic acid-induced neurodegeneration
title_full_unstemmed c-Jun N-terminal Kinase (JNK) induces phosphorylation of amyloid precursor protein (APP) at Thr668, in okadaic acid-induced neurodegeneration
title_short c-Jun N-terminal Kinase (JNK) induces phosphorylation of amyloid precursor protein (APP) at Thr668, in okadaic acid-induced neurodegeneration
title_sort c-jun n-terminal kinase (jnk) induces phosphorylation of amyloid precursor protein (app) at thr668, in okadaic acid-induced neurodegeneration
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5032005/
https://www.ncbi.nlm.nih.gov/pubmed/26839154
http://dx.doi.org/10.5483/BMBRep.2016.49.7.246
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