Published online Mar 19, 2024. doi: 10.5498/wjp.v14.i3.445
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
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.
The precise pathological mechanisms that underlie the correlation between insulin resistance and AD remain elusive.
This study aims to investigate the impact of KAT7, a histone acetyltransferase involved in regulating multiple genes, on insulin resistance in AD.
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.
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.
Our study revealed that upregulation of KAT7 restored insulin sensitivity in AD by recruiting HMGN1 to augment acetylation of the DYRK1A gene.
Our findings highlight KAT7 as a novel and promising therapeutic target for addressing insulin resistance in AD.