13-Docosenamide Enhances Oligodendrocyte Precursor Cell Differentiation via USP33-Mediated Deubiquitination of CNR1 in Chronic Cerebral Hypoperfusion.
10.1007/s12264-025-01461-w
- Author:
Yuhao XU
1
;
Yi TAN
1
;
Zhi ZHANG
1
;
Duo CHEN
1
;
Chao ZHOU
1
;
Liang SUN
1
;
Shengnan XIA
1
;
Xinyu BAO
1
;
Haiyan YANG
1
;
Yun XU
2
Author Information
1. Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 212008, China.
2. Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 212008, China. xuyun20042001@aliyun.com.
- Publication Type:Journal Article
- Keywords:
13-Docosenamide;
Cannabinoid receptor 1;
Oligodendrocyte precursor cell;
Ubiquitin-specific peptidase 33;
White matter injury
- MeSH:
Animals;
Oligodendrocyte Precursor Cells/metabolism*;
Mice;
Cell Differentiation/drug effects*;
Male;
Receptor, Cannabinoid, CB1/metabolism*;
Mice, Inbred C57BL;
Ubiquitin Thiolesterase/metabolism*;
Ubiquitination/drug effects*;
Carotid Stenosis/complications*;
Cognitive Dysfunction/drug therapy*
- From:
Neuroscience Bulletin
2025;41(11):1939-1956
- CountryChina
- Language:English
-
Abstract:
Chronic cerebral hypoperfusion leads to white matter injury (WMI), which plays a significant role in contributing to vascular cognitive impairment. While 13-docosenamide is a type of fatty acid amide, it remains unclear whether it has therapeutic effects on chronic cerebral hypoperfusion. In this study, we conducted bilateral common carotid artery stenosis (BCAS) surgery to simulate chronic cerebral hypoperfusion-induced WMI and cognitive impairment. Our findings showed that 13-docosenamide alleviates WMI and cognitive impairment in BCAS mice. Mechanistically, 13-docosenamide specifically binds to cannabinoid receptor 1 (CNR1) in oligodendrocyte precursor cells (OPCs). This interaction results in an upregulation of ubiquitin-specific peptidase 33 (USP33)-mediated CNR1 deubiquitination, subsequently increasing CNR1 protein expression, activating the phosphorylation of the AKT/mTOR pathway, and promoting the differentiation of OPCs. In conclusion, our study suggests that 13-docosenamide can ameliorate chronic cerebral hypoperfusion-induced WMI and cognitive impairment by enhancing OPC differentiation and could serve as a potential therapeutic drug.
