Inhibition of Histone Acetylation by ANP32A Induces Memory Deficits

Article type: Research Article

Authors: Chai, Gao-Shang^{a; c; 1} | Feng, Qiong^{b; c; 1} | Ma, Rong-Hong^{d; 1} | Qian, Xiao-Hang^a | Luo, Dan-Ju^e | Wang, Zhi-Hao^c | Hu, Yu^c | Sun, Dong-Sheng^c | Zhang, Jun-Fei^c | Li, Xiao^c | Li, Xiao-Guang^c | Ke, Dan^c | Wang, Jian-Zhi^{c; f} | Yang, Xi-Fei^{g; *} | Liu, Gong-Ping^{c; f; *}

Affiliations: [a] Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, P. R. China | [b] Department of Pathology, Wuhan Children’s Hospital, Wuhan, P. R. China | [c] Department of Pathophysiology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Key Laboratory of Ministry of Education of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China | [d] Department of Laboratory Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China | [e] Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China | [f] Co-innovation Center of Neuroregeneration, Nantong University, Nantong, JS, China | [g] Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Longyuan Road, Nanshan District, Shenzhen, China

Correspondence: [*] Correspondence to: Gong-Ping Liu, Department of Pathophysiology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Key Laboratory of Ministry of Education of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P. R. China. Tel.: +86 027 83692625; liugp111@mail.hust.edu.cn and Xi-Fei Yang, Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, No.8, Longyuan Road, Nanshan District, Shenzhen 518055, China. E-mail: xifeiyang@gmail.com.

Note: [1] These authors contributed equally to this work.

Abstract: There is accumulating evidence that decreased histone acetylation is involved in normal aging and neurodegenerative diseases. Recently, we found that ANP32A, a key component of INHAT (inhibitor of acetyltransferases) that suppresses histone acetylation, increased in aged and cognitively impaired C57 mice and expressing wild-type human full length tau (htau) transgenic mice. Downregulating ANP32A restored cognitive function and synaptic plasticity through upregulation of the expressions of synaptic-related proteins via increasing histone acetylation. However, there is no direct evidence that ANP32A can induce neurodegeneration and memory deficits. In the present study, we overexpressed ANP32A in the hippocampal CA3 region of C57 mice and found that ANP32A overexpression induced cognitive abilities and synaptic plasticity deficits, with decreased synaptic-related protein expression and histone acetylation. Combined with our recent studies, our findings reveal that upregulated ANP32A induced-suppressing histone acetylation may underlie the cognitive decline in neurodegenerative disease, and suppression of ANP32A may represent a promising therapeutic approach for neurodegenerative diseases including Alzheimer’s disease.

Keywords: Alzheimer’s disease, ANP32A, cognition, histone acetylation, synaptic-related protein

DOI: 10.3233/JAD-180090

Journal: Journal of Alzheimer's Disease, vol. 63, no. 4, pp. 1537-1546, 2018