AQUILI Luca    所属   立命館アジア太平洋大学  国際経営学部    職種   准教授
言語種別	英語
発行・発表の年月	2025
形態種別	学術論文
査読	査読あり
標題	Homeostatic DNMT3a activity is required to restore cognition and hippocampal DNA methylation in the 5xFAD model of Alzheimer’s disease
執筆形態	分担
掲載誌名	Aging and Disease
掲載区分	国外
巻・号・頁	17(5)
著者・共著者	Yanzhi Liu, Chi Him Poon, Long Sum Rachel Tse, Jaydeep Roy, Charlotte Theodora So, Benjamin Chun-Kit Tong, Kwok-Ming Yao, George Lim Tipoe, Harry WM Steinbusch, Luca Aquili, King-Ho Cheung, Man-Lung Fung, Lee Wei Lim
概要	This 5xFAD mouse study tested whether restoring DNA methylation with prolonged L-methionine treatment can improve Alzheimer-related pathology and cognition. Treatment rescued spatial memory, reduced amyloid burden and neuroinflammation, restored plasticity-related molecules, and enhanced serotonergic signaling. DNMT3a knockdown weakened these benefits and impaired memory in both wild-type and 5xFAD mice. Importantly, DNMT3a overexpression was also detrimental. The results show that cognitive function depends on balanced, homeostatic DNMT3a activity rather than simple maximization, while supporting methyl supplementation for carefully selected hypomethylated disease states.
DOI	https://doi.org/10.14336/AD.2025.0283