Lu QS, Ma L, Jiang WJ, Wang XB, Lu M. KAT7/HMGN1 signaling epigenetically induces tyrosine phosphorylation-regulated kinase 1A expression to ameliorate insulin resistance in Alzheimer’s disease. World J Psychiatry 2024; 14(3): 445-455 [PMID: 38617985 DOI: 10.5498/wjp.v14.i3.445]
Corresponding Author of This Article
Mei Lu, MD, Professor, Department of Geriatric Medicine, Qilu Hospital of Shandong University, No. 107 Wenhua Xilu, Jinan 250012, Shandong Province, China. lumei@qiluhospital.com
Research Domain of This Article
Psychiatry
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Psychiatry. Mar 19, 2024; 14(3): 445-455 Published online Mar 19, 2024. doi: 10.5498/wjp.v14.i3.445
KAT7/HMGN1 signaling epigenetically induces tyrosine phosphorylation-regulated kinase 1A expression to ameliorate insulin resistance in Alzheimer’s disease
Qun-Shan Lu, Lin Ma, Wen-Jing Jiang, Xing-Bang Wang, Mei Lu
Qun-Shan Lu, Lin Ma, Wen-Jing Jiang, Xing-Bang Wang, Mei Lu, Department of Geriatric Medicine, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
Lin Ma, Wen-Jing Jiang, Xing-Bang Wang, Mei Lu, Key Laboratory of Cardiovascular Proteomics of Shandong Province, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
Author contributions: Lu QS and Lu M designed the study; Lu QS, Ma L, Jiang WJ, and Wang XB performed the experiments; Lu QS and Lu M wrote the manuscript.
Supported byNatural Science Foundation of Shandong Province, No. ZR2020MH147; and National Natural Science Foundation of China, No. 82002343.
Institutional review board statement: All experiments were performed under the authorization and guidelines of Ethics Committee of Qilu Hospital of Shandong University, No. KYLL-2020 (KS)-102.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Shandong University, No. MDL2021-08-17-02.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: Further information and requests for resources and reagents should be directed to and will be fulfilled by the corresponding author at lumei@qiluhospital.com.
ARRIVE guidelines statement: The authors have read the ARRIVE Guidelines, and the manuscript was prepared and revised according to the ARRIVE Guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Mei Lu, MD, Professor, Department of Geriatric Medicine, Qilu Hospital of Shandong University, No. 107 Wenhua Xilu, Jinan 250012, Shandong Province, China. lumei@qiluhospital.com
Received: November 30, 2023 Peer-review started: November 30, 2023 First decision: December 18, 2023 Revised: December 31, 2023 Accepted: February 1, 2024 Article in press: February 1, 2024 Published online: March 19, 2024 Processing time: 110 Days and 2.3 Hours
ARTICLE HIGHLIGHTS
Research background
Epidemiological studies increasingly suggest a significant connection between Alzheimer's disease (AD) and type 2 diabetes mellitus, primarily attributed to insulin resistance, a prominent and pivotal pathological characteristic.
Research motivation
The precise pathological mechanisms that underlie the correlation between insulin resistance and AD remain elusive.
Research objectives
This study aims to investigate the impact of KAT7, a histone acetyltransferase involved in regulating multiple genes, on insulin resistance in AD.
Research methods
APPswe/PS1-dE9 transgenic mice were employed to study AD, while db/db mice were utilized as a model for diabetes. An in vitro AD model was established through Aβ stimulation.
Research results
Overexpression of KAT7 decreased Aβ accumulation, alleviated ferroptosis and apoptosis in brain tissues and neurons. KAT7 epigenetically regulated the expression of DYRK1A via recruiting the HMGN1 and activated AKT and GSK3β to alleviate insulin resistance.
Research conclusions
Our study revealed that upregulation of KAT7 restored insulin sensitivity in AD by recruiting HMGN1 to augment acetylation of the DYRK1A gene.
Research perspectives
Our findings highlight KAT7 as a novel and promising therapeutic target for addressing insulin resistance in AD.
