USP47 Regulates Excitatory Synaptic Plasticity and Modulates Seizures in Murine Models by Blocking Ubiquitinated AMPAR Degradation.
10.1007/s12264-025-01441-0
- Author:
Juan YANG
1
;
Haiqing ZHANG
2
;
You WANG
1
;
Yuemei LUO
2
;
Weijin ZHENG
3
;
Yong LIU
1
;
Qian JIANG
1
;
Jing DENG
1
;
Qiankun LIU
1
;
Peng ZHANG
1
;
Hao HUANG
2
;
Changyin YU
4
,
5
;
Zucai XU
6
;
Yangmei CHEN
7
Author Information
1. Department of Neurology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
2. Department of Neurology, Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, China.
3. Department of Health Management, Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, China.
4. Department of Neurology, Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, China. yuchangyin68@
5. com.
6. Department of Neurology, Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, China. docxzc@zmu.edu.cn.
7. Department of Neurology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China. 300249@cqmu.edu.cn.
- Publication Type:Journal Article
- Keywords:
Epilepsy;
Glutamate receptor 1;
Protein degradation;
Synaptic plasticity;
Ubiquitin-specific protease 47
- MeSH:
Animals;
Receptors, AMPA/metabolism*;
Neuronal Plasticity/physiology*;
Seizures/physiopathology*;
Disease Models, Animal;
Mice, Inbred C57BL;
Mice;
Ubiquitin Thiolesterase/genetics*;
Male;
Excitatory Postsynaptic Potentials/physiology*;
Ubiquitination;
Dendritic Spines/metabolism*;
Hippocampus/metabolism*
- From:
Neuroscience Bulletin
2025;41(10):1805-1823
- CountryChina
- Language:English
-
Abstract:
Epilepsy is a chronic neurological disorder affecting ~65 million individuals worldwide. Abnormal synaptic plasticity is one of the most important pathological features of this condition. We investigated how ubiquitin-specific peptidase 47 (USP47) influences synaptic plasticity and its link to epilepsy. We found that USP47 enhanced excitatory postsynaptic transmission and increased the density of total dendritic spines and the proportion of mature dendritic spines. Furthermore, USP47 inhibited the degradation of the ubiquitinated α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunit glutamate receptor 1 (GluR1), which is associated with synaptic plasticity. In addition, elevated levels of USP47 were found in epileptic mice, and USP47 knockdown reduced the frequency and duration of seizure-like events and alleviated epileptic seizures. To summarize, we present a new mechanism whereby USP47 regulates excitatory postsynaptic plasticity through the inhibition of ubiquitinated GluR1 degradation. Modulating USP47 may offer a potential approach for controlling seizures and modifying disease progression in future therapeutic strategies.
