Cited 17 time in webofscience Cited 16 time in scopus

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
Authors
Choi, HeesunKim, Haeng JunYang, JinheeChae, SehyunLee, WonikChung, SunwooKim, JisooChoi, HyunjungSong, HyeseungLee, Chang KonJun, Jae HyunLee, Yong JaeLee, KyunghyeonKim, SemiSim, Hye-riChoi, Young IlRyu, Keun HoPark, Jong-ChanLee, DongjoonHan, Sun-HoHwang, DaeheeKyung, JangbeenMook-Jung, Inhee
DGIST Authors
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
Issue Date
2020-01
Citation
Aging Cell, 19(1)
Type
Article
Article Type
Article
Author Keywords
Alzheimer&aposs diseaseneurodegenerative diseasestautau interactometau post-translational modification
Keywords
MOTIFSHDAC6
ISSN
1474-9718
Abstract
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.
URI
http://hdl.handle.net/20.500.11750/11021
DOI
10.1111/acel.13081
Publisher
Wiley
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