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Acetylation changes tau interactome to degrade tau in Alzheimer’s disease animal and organoid models
Alzheimer's disease (AD) is an age‐related neurodegenerative disease. The most common pathological hallmarks are amyloid plaques and neurofibrillary tangles in the brain. In the brains of patients with AD, pathological tau is abnormally accumulated causing neuronal loss, synaptic dysfunction, a...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6974726/ https://www.ncbi.nlm.nih.gov/pubmed/31763743 http://dx.doi.org/10.1111/acel.13081 |
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author | Choi, Heesun Kim, Haeng Jun Yang, Jinhee Chae, Sehyun Lee, Wonik Chung, Sunwoo Kim, Jisoo Choi, Hyunjung Song, Hyeseung Lee, Chang Kon Jun, Jae Hyun Lee, Yong Jae Lee, Kyunghyeon Kim, Semi Sim, Hye‐ri Choi, Young Il Ryu, Keun Ho Park, Jong‐Chan Lee, Dongjoon Han, Sun‐Ho Hwang, Daehee Kyung, Jangbeen Mook‐Jung, Inhee |
author_facet | Choi, Heesun Kim, Haeng Jun Yang, Jinhee Chae, Sehyun Lee, Wonik Chung, Sunwoo Kim, Jisoo Choi, Hyunjung Song, Hyeseung Lee, Chang Kon Jun, Jae Hyun Lee, Yong Jae Lee, Kyunghyeon Kim, Semi Sim, Hye‐ri Choi, Young Il Ryu, Keun Ho Park, Jong‐Chan Lee, Dongjoon Han, Sun‐Ho Hwang, Daehee Kyung, Jangbeen Mook‐Jung, Inhee |
author_sort | Choi, Heesun |
collection | PubMed |
description | Alzheimer's disease (AD) is an age‐related neurodegenerative disease. The most common pathological hallmarks are amyloid plaques and neurofibrillary tangles in the brain. In the brains of patients with AD, pathological tau is abnormally accumulated causing neuronal loss, synaptic dysfunction, and cognitive decline. We found a histone deacetylase 6 (HDAC6) inhibitor, CKD‐504, changed the tau interactome dramatically to degrade pathological tau not only in AD animal model (ADLP(APT)) brains containing both amyloid plaques and neurofibrillary tangles but also in AD patient‐derived brain organoids. Acetylated tau recruited chaperone proteins such as Hsp40, Hsp70, and Hsp110, and this complex bound to novel tau E3 ligases including UBE2O and RNF14. This complex degraded pathological tau through proteasomal pathway. We also identified the responsible acetylation sites on tau. These dramatic tau‐interactome changes may result in tau degradation, leading to the recovery of synaptic pathology and cognitive decline in the ADLP(APT) mice. |
format | Online Article Text |
id | pubmed-6974726 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-69747262020-01-28 Acetylation changes tau interactome to degrade tau in Alzheimer’s disease animal and organoid models Choi, Heesun Kim, Haeng Jun Yang, Jinhee Chae, Sehyun Lee, Wonik Chung, Sunwoo Kim, Jisoo Choi, Hyunjung Song, Hyeseung Lee, Chang Kon Jun, Jae Hyun Lee, Yong Jae Lee, Kyunghyeon Kim, Semi Sim, Hye‐ri Choi, Young Il Ryu, Keun Ho Park, Jong‐Chan Lee, Dongjoon Han, Sun‐Ho Hwang, Daehee Kyung, Jangbeen Mook‐Jung, Inhee Aging Cell Original Papers Alzheimer's disease (AD) is an age‐related neurodegenerative disease. The most common pathological hallmarks are amyloid plaques and neurofibrillary tangles in the brain. In the brains of patients with AD, pathological tau is abnormally accumulated causing neuronal loss, synaptic dysfunction, and cognitive decline. We found a histone deacetylase 6 (HDAC6) inhibitor, CKD‐504, changed the tau interactome dramatically to degrade pathological tau not only in AD animal model (ADLP(APT)) brains containing both amyloid plaques and neurofibrillary tangles but also in AD patient‐derived brain organoids. Acetylated tau recruited chaperone proteins such as Hsp40, Hsp70, and Hsp110, and this complex bound to novel tau E3 ligases including UBE2O and RNF14. This complex degraded pathological tau through proteasomal pathway. We also identified the responsible acetylation sites on tau. These dramatic tau‐interactome changes may result in tau degradation, leading to the recovery of synaptic pathology and cognitive decline in the ADLP(APT) mice. John Wiley and Sons Inc. 2019-11-25 2020-01 /pmc/articles/PMC6974726/ /pubmed/31763743 http://dx.doi.org/10.1111/acel.13081 Text en © 2019 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Papers Choi, Heesun Kim, Haeng Jun Yang, Jinhee Chae, Sehyun Lee, Wonik Chung, Sunwoo Kim, Jisoo Choi, Hyunjung Song, Hyeseung Lee, Chang Kon Jun, Jae Hyun Lee, Yong Jae Lee, Kyunghyeon Kim, Semi Sim, Hye‐ri Choi, Young Il Ryu, Keun Ho Park, Jong‐Chan Lee, Dongjoon Han, Sun‐Ho Hwang, Daehee Kyung, Jangbeen Mook‐Jung, Inhee Acetylation changes tau interactome to degrade tau in Alzheimer’s disease animal and organoid models |
title | Acetylation changes tau interactome to degrade tau in Alzheimer’s disease animal and organoid models |
title_full | Acetylation changes tau interactome to degrade tau in Alzheimer’s disease animal and organoid models |
title_fullStr | Acetylation changes tau interactome to degrade tau in Alzheimer’s disease animal and organoid models |
title_full_unstemmed | Acetylation changes tau interactome to degrade tau in Alzheimer’s disease animal and organoid models |
title_short | Acetylation changes tau interactome to degrade tau in Alzheimer’s disease animal and organoid models |
title_sort | acetylation changes tau interactome to degrade tau in alzheimer’s disease animal and organoid models |
topic | Original Papers |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6974726/ https://www.ncbi.nlm.nih.gov/pubmed/31763743 http://dx.doi.org/10.1111/acel.13081 |
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