Targeting G-quadruplexes in an ageing epigenetic regulator promoter for rescuing mitochondrial dysfunction in Alzheimer's disease

Jie Yang; Geng Qin; Jingsheng Niu; Yue Wei; Xuexia Li; Chuanqi Zhao; Chunyu Wang; Jinsong Ren; Xiaogang Qu

doi:10.1039/d2cc05957f

Targeting G-quadruplexes in an ageing epigenetic regulator promoter for rescuing mitochondrial dysfunction in Alzheimer's disease

Chem Commun (Camb). 2023 Jan 24;59(8):1078-1081. doi: 10.1039/d2cc05957f.

Authors

Jie Yang^{1

2}, Geng Qin^{1

2}, Jingsheng Niu^{1

2}, Yue Wei^{1

2}, Xuexia Li^{1

2}, Chuanqi Zhao^{1

2}, Chunyu Wang³, Jinsong Ren^{1

2}, Xiaogang Qu^{1

2}

Affiliations

¹ Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, P. R. China. xqu@ciac.ac.cn.
² School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, Anhui 230026, P. R. China.
³ State Key Laboratory of Supramolecular Structure and Materials, Jilin University, Changchun 130012, China.

PMID: 36621881
DOI: 10.1039/d2cc05957f

Abstract

Here, we provide an out-of-the-box G-quadruplex (G4) targeting-based strategy for rescuing mitochondrial dysfunction in Alzheimer's disease. We predict and verify the presence of G4s within the promoter of an ageing epigenetic regulator BAZ2B. G4-specific ligands targeting BAZ2B G4s could significantly down-regulate the BAZ2B expression and relieve mitochondrial dysfunction. Therefore, this work may provide a new way of rescuing mitochondrial dysfunction in AD by targeting G4s in a specific ageing epigenetic regulator promoter.

MeSH terms

Alzheimer Disease*
Epigenesis, Genetic
G-Quadruplexes*
Humans
Ligands
Mitochondria
Promoter Regions, Genetic
Transcription Factors, General*

Substances

Ligands
BAZ2B protein, human
Transcription Factors, General