The deacetylase SIRT6 reduces amyloid pathology and supports cognition in mice by reducing the stability of APP in neurons.

Rong Cheng, Ning Bai, Shuhui Liu, Xiong Zhao, Bo Jiang, Wendong Guo, Sunrun Cao, Jingwei Liu, Na Li, Xiaoman Li, Xuan Wu, Fei Yi, Zhuo Wang, Qiqiang Guo, Jiayi Wei, Ming Bai, Xiaoyou Jiang, Xiaoyu Song, Zhuo Wang, Qi Miao, Difei Wang, Yu Di, Hua Liu, Liu Cao

College of Basic Medical Science, Health Sciences Institute, China Medical University, Shenyang, Liaoning 110122, China.College of Basic Medical Science, Health Sciences Institute, China Medical University, Shenyang, Liaoning 110122, China. · pubmed

Paper

Abstract

Alzheimer's disease (AD) is an aging-related neurodegenerative disorder that results in progressively impaired memory and is often associated with amyloid plaques. Previous studies implicate the deacetylases SIRT1 and SIRT2 in regulating the processing of amyloid precursor protein (APP). Here, we investigated whether APP is regulated by the related deacetylase SIRT6, which shows aging-associated decreases in activity. We found that the abundance of SIRT6 was reduced in the cortex and hippocampus of aged and AD model mice and negatively correlated with that of APP. In mouse hippocampal neurons and transfected human cells, SIRT6 interacted with and deacetylated APP at three consecutive Lys residues (Lys

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Research summary

The paper investigates the role of SIRT6 in regulating amyloid precursor protein (APP) and its implications for Alzheimer's disease, which is indeed an age-related condition. However, the focus is primarily on the pathology and treatment of symptoms rather than addressing the root causes of aging or lifespan extension. The findings contribute to understanding the molecular mechanisms involved in AD but do not significantly advance the field of longevity research. Thus, while it is relevant, its impact is limited.

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