期刊
AGING CELL
卷 19, 期 1, 页码 -出版社
WILEY
DOI: 10.1111/acel.13081
关键词
Alzheimer's disease; neurodegenerative diseases; tau; tau interactome; tau post-translational modification
资金
- Institute for Basic Science [IBS-R013-A1]
- National Research Foundation of Korea [2018R1A2A1A19019062, 2018R1A5A2025964]
- Korea Health Industry Development Institute [HI18C0630]
- Chong Kun Dang Pharmaceutical Corp
- Ministry of Health Welfare
- National Research Foundation of Korea [2018R1A2A1A19019062] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据