Deciphering the Role of N-Acetyltransferase 10 in Thalamic Hemorrhage Through Integrative Multi-Omics and Experimental Validation
Year: 2025
Type: article
Abstract: BACKGROUND: Thalamic hemorrhage (TH) is a severe neurological condition, the molecular mechanisms of which are poorly understood, particularly in clinical settings. N-acetyltransferase 10 (NAT10), a regulator of RNA N4-acetylcytidine (ac4C) modification, has been implicated in cell cycle regulation and identified as a potential therapeutic target. This study explored the effects of NAT10 inhibition on TH pathology using a multi-omics approach. METHODS: A mouse model of TH was established via collagenase IV injection. NAT10 activity was detected by dot blot and inhibited using Remodelin. Comprehensive multi-omics analyses, including 16S ribosomal Deoxyribonucleic Acid (16S rDNA) sequencing, metabolomics, and transcriptomics, were used. Behavioral, histological, and molecular evaluations were conducted to evaluate the key genes. RESULTS: ) genes were linked to xanthine, which is a key metabolite implicated in TH pathology. Based on these findings, the xanthine oxidase inhibitor febuxostat was tested, demonstrating significant therapeutic benefits in TH-affected mice. Behavioral, histological, and molecular evaluations confirmed that NAT10 inhibition alleviated TH-induced damage. CONCLUSIONS: This study provides the first comprehensive molecular insights into the therapeutic potential of NAT10 inhibition in TH. Moreover, it identified NAT10 inhibitors and febuxostat as promising candidates for TH management, paving the way for future therapeutic development targeting NAT10 in this condition.
DOI: 10.31083/jin44643
Authors: Yaqun Li, Ju Gao, Yinggang Xiao, Tianfeng Huang
Institutions: Northern Jiangsu People's Hospital, Yangzhou University
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,900
Awards: G2529405562, G7936192605
OpenAlex ID: W4417075553