SIRT1和SIRT2对APP乙酰化的协同作用

IF 8 1区 医学 Q1 CELL BIOLOGY
Aging Cell Pub Date : 2023-08-21 DOI:10.1111/acel.13967
Na Li, Ning Bai, Xiong Zhao, Rong Cheng, Xuan Wu, Bo Jiang, Xiaoman Li, Mingli Xue, Hongde Xu, Qiqiang Guo, Wendong Guo, Mengtao Ma, Sunrun Cao, Yanling Feng, Xiaoyu Song, Zhuo Wang, Xiaoyu Zhang, Yu Zou, Difei Wang, Hua Liu, Liu Cao
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引用次数: 1

摘要

阿尔茨海默病(AD)是一种与年龄相关的神经退行性疾病,其特征是淀粉样蛋白-β(Aβ)沉积和神经原纤维缠结。尽管NAD+依赖性脱乙酰酶SIRT1和SIRT2在年龄相关疾病中发挥着关键作用,但它们在AD中的协同作用尚未阐明。在此,我们报道了SIRT2:SIRT1比率在衰老小鼠和AD小鼠模型中升高。在HT22小鼠海马神经元细胞中,Aβ激发与SIRT1表达减少相关,而SIRT2表达增加。SIRT1的过度表达可防止Aβ诱导的神经毒性。我们发现SIRT1通过抑制SIRT2与APP的结合来阻止SIRT2介导的APP脱乙酰化。SIRT1的缺失减少了APP再循环回细胞表面,并促进APP向内体过渡,从而有助于APP的淀粉样蛋白生成过程。我们的研究结果确定了SIRT1通过抑制SIRT2脱乙酰基来进行神经保护的机制,并为AD的治疗干预提供了一条有前景的途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Cooperative effects of SIRT1 and SIRT2 on APP acetylation

Cooperative effects of SIRT1 and SIRT2 on APP acetylation

Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by amyloid-β (Aβ) deposition and neurofibrillary tangles. Although the NAD+-dependent deacetylases SIRT1 and SIRT2 play pivotal roles in age-related diseases, their cooperative effects in AD have not yet been elucidated. Here, we report that the SIRT2:SIRT1 ratio is elevated in the brains of aging mice and in the AD mouse models. In HT22 mouse hippocampal neuronal cells, Aβ challenge correlates with decreased SIRT1 expression, while SIRT2 expression is increased. Overexpression of SIRT1 prevents Aβ-induced neurotoxicity. We find that SIRT1 impedes SIRT2-mediated APP deacetylation by inhibiting the binding of SIRT2 to APP. Deletion of SIRT1 reduces APP recycling back to the cell surface and promotes APP transiting toward the endosome, thus contributing to the amyloidogenic processing of APP. Our findings define a mechanism for neuroprotection by SIRT1 through suppression of SIRT2 deacetylation, and provide a promising avenue for therapeutic intervention of AD.

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来源期刊
Aging Cell
Aging Cell Biochemistry, Genetics and Molecular Biology-Cell Biology
自引率
2.60%
发文量
212
期刊介绍: Aging Cell is an Open Access journal that focuses on the core aspects of the biology of aging, encompassing the entire spectrum of geroscience. The journal's content is dedicated to publishing research that uncovers the mechanisms behind the aging process and explores the connections between aging and various age-related diseases. This journal aims to provide a comprehensive understanding of the biological underpinnings of aging and its implications for human health. The journal is widely recognized and its content is abstracted and indexed by numerous databases and services, which facilitates its accessibility and impact in the scientific community. These include: Academic Search (EBSCO Publishing) Academic Search Alumni Edition (EBSCO Publishing) Academic Search Premier (EBSCO Publishing) Biological Science Database (ProQuest) CAS: Chemical Abstracts Service (ACS) Embase (Elsevier) InfoTrac (GALE Cengage) Ingenta Select ISI Alerting Services Journal Citation Reports/Science Edition (Clarivate Analytics) MEDLINE/PubMed (NLM) Natural Science Collection (ProQuest) PubMed Dietary Supplement Subset (NLM) Science Citation Index Expanded (Clarivate Analytics) SciTech Premium Collection (ProQuest) Web of Science (Clarivate Analytics) Being indexed in these databases ensures that the research published in Aging Cell is discoverable by researchers, clinicians, and other professionals interested in the field of aging and its associated health issues. This broad coverage helps to disseminate the journal's findings and contributes to the advancement of knowledge in geroscience.
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