SRC-1对衰老相关认知衰退的保护作用。

A protective role of SRC-1 against aging associated cognitive decline.

作者信息

Liu Hesong, Yang Yongjie, Bean Jonathan C, He Yang, Liu Hailan, Majji Rambabu, Liang Chen, Zhang Nan, Yu Meng, Tu Longlong, Liu Qingzhuo, Deng Yue, Conde Kristine M, Yin Na, Wang Mengjie, Li Yongxiang, Han Junying, Jossy Sanika Vattakuzhiyil, Burt Megan Elyse, Yalamanchili Hari Krishna, Wang Chunmei

机构信息

USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.

Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, USA.

出版信息

Aging (Albany NY). 2025 Aug 27;17(8):2167-2188. doi: 10.18632/aging.206311.

DOI:10.18632/aging.206311

PMID:40882002

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12422791/

Abstract

INTRODUCTION

Research indicates a strong correlation between obesity and the risk of dementia, both are linked to steroid receptor coactivator-1 (SRC-1), a transcriptional coactivator.

METHODS

We used RNA sequencing analysis (RNA-Seq) to investigate the transcriptome of SRC-1-KO mice, and identified S100 calcium-binding protein A6 (S100A6), an AD associated gene, as one target of SRC-1. We tested cognitive behaviors in SRC-1-KO mice and mice with a humanized SRC-1 mutation (SRC-1), and performed promoter luciferase assays on S100A6.

RESULTS

Loss of SRC-1 caused alterations in gene signatures that are commonly associated with neurodegenerative diseases, including AD, and diminished the neural plasticity of the hippocampal CA1 neurons. Both SRC-1-KO and SRC-1 mice displayed early signs of contextual memory impairment at 6 months of age. Mechanistically, SRC-1 significantly promoted the expression S100A6.

CONCLUSION

We identified a protective role of SRC1 against aging associated cognitive decline, potentially by promoting the expression of S100A6.

摘要

引言

研究表明肥胖与痴呆风险之间存在强相关性，二者均与类固醇受体辅激活因子-1（SRC-1，一种转录辅激活因子）有关。

方法

我们使用RNA测序分析（RNA-Seq）来研究SRC-1基因敲除小鼠的转录组，并确定了与阿尔茨海默病相关的基因S100钙结合蛋白A6（S100A6）是SRC-1的一个靶点。我们测试了SRC-1基因敲除小鼠和携带人源化SRC-1突变的小鼠（SRC-1）的认知行为，并对S100A6进行了启动子荧光素酶测定。