PMID- 36654858
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230120
IS  - 2589-0042 (Electronic)
IS  - 2589-0042 (Linking)
VI  - 26
IP  - 1
DP  - 2023 Jan 20
TI  - Downregulation of UBE4B promotes CNS axon regrowth and functional recovery after 
      stroke.
PG  - 105885
LID - 10.1016/j.isci.2022.105885 [doi]
LID - 105885
AB  - The limited intrinsic regrowth capacity of corticospinal axons impedes functional 
      recovery after cortical stroke. Although the mammalian target of rapamycin (mTOR) 
      and p53 pathways have been identified as the key intrinsic pathways regulating 
      CNS axon regrowth, little is known about the key upstream regulatory mechanism by 
      which these two major pathways control CNS axon regrowth. By screening genes that 
      regulate ubiquitin-mediated degradation of the p53 proteins in mice, we found 
      that ubiquitination factor E4B (UBE4B) represses axonal regrowth in retinal 
      ganglion cells and corticospinal neurons. We found that axonal regrowth induced 
      by UBE4B depletion depended on the cooperative activation of p53 and mTOR. 
      Importantly, overexpression of UbV.E4B, a competitive inhibitor of UBE4B, in 
      corticospinal neurons promoted corticospinal axon sprouting and facilitated the 
      recovery of corticospinal axon-dependent function in a cortical stroke model. 
      Thus, our findings provide a translatable strategy for restoring corticospinal 
      tract-dependent functions after cortical stroke.
CI  - (c) 2022 The Author(s).
FAU - Jin, Shuang
AU  - Jin S
AD  - Department of Neurobiology and Department of Rehabilitation Medicine, First 
      Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 
      Province 310003, P.R. China.
AD  - Liangzhu Laboratory, MOE Frontier Science Center for Brain Science and 
      Brain-Machine Integration, State Key Laboratory of Brain-Machine Intelligence, 
      Zhejiang University, 1369 West Wenyi Road, Hangzhou 311121, P.R. China.
AD  - NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, 
      Hangzhou 310058, P.R. China.
FAU - Chen, Xiangfeng
AU  - Chen X
AD  - Department of Neurobiology and Department of Rehabilitation Medicine, First 
      Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 
      Province 310003, P.R. China.
AD  - Liangzhu Laboratory, MOE Frontier Science Center for Brain Science and 
      Brain-Machine Integration, State Key Laboratory of Brain-Machine Intelligence, 
      Zhejiang University, 1369 West Wenyi Road, Hangzhou 311121, P.R. China.
AD  - NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, 
      Hangzhou 310058, P.R. China.
FAU - Zheng, Hanyu
AU  - Zheng H
AD  - Department of Neurobiology and Department of Rehabilitation Medicine, First 
      Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 
      Province 310003, P.R. China.
AD  - Liangzhu Laboratory, MOE Frontier Science Center for Brain Science and 
      Brain-Machine Integration, State Key Laboratory of Brain-Machine Intelligence, 
      Zhejiang University, 1369 West Wenyi Road, Hangzhou 311121, P.R. China.
AD  - NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, 
      Hangzhou 310058, P.R. China.
FAU - Cai, Wanxiong
AU  - Cai W
AD  - Department of Neurobiology and Department of Rehabilitation Medicine, First 
      Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 
      Province 310003, P.R. China.
AD  - Liangzhu Laboratory, MOE Frontier Science Center for Brain Science and 
      Brain-Machine Integration, State Key Laboratory of Brain-Machine Intelligence, 
      Zhejiang University, 1369 West Wenyi Road, Hangzhou 311121, P.R. China.
AD  - NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, 
      Hangzhou 310058, P.R. China.
FAU - Lin, Xurong
AU  - Lin X
AD  - Department of Neurobiology and Department of Rehabilitation Medicine, First 
      Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 
      Province 310003, P.R. China.
AD  - Liangzhu Laboratory, MOE Frontier Science Center for Brain Science and 
      Brain-Machine Integration, State Key Laboratory of Brain-Machine Intelligence, 
      Zhejiang University, 1369 West Wenyi Road, Hangzhou 311121, P.R. China.
AD  - NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, 
      Hangzhou 310058, P.R. China.
FAU - Kong, Xiangxing
AU  - Kong X
AD  - Department of Neurobiology and Department of Rehabilitation Medicine, First 
      Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 
      Province 310003, P.R. China.
AD  - Liangzhu Laboratory, MOE Frontier Science Center for Brain Science and 
      Brain-Machine Integration, State Key Laboratory of Brain-Machine Intelligence, 
      Zhejiang University, 1369 West Wenyi Road, Hangzhou 311121, P.R. China.
AD  - NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, 
      Hangzhou 310058, P.R. China.
FAU - Ni, Yingchun
AU  - Ni Y
AD  - Department of Neurobiology and Department of Rehabilitation Medicine, First 
      Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 
      Province 310003, P.R. China.
AD  - Liangzhu Laboratory, MOE Frontier Science Center for Brain Science and 
      Brain-Machine Integration, State Key Laboratory of Brain-Machine Intelligence, 
      Zhejiang University, 1369 West Wenyi Road, Hangzhou 311121, P.R. China.
AD  - NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, 
      Hangzhou 310058, P.R. China.
FAU - Ye, Jingjia
AU  - Ye J
AD  - Liangzhu Laboratory, MOE Frontier Science Center for Brain Science and 
      Brain-Machine Integration, State Key Laboratory of Brain-Machine Intelligence, 
      Zhejiang University, 1369 West Wenyi Road, Hangzhou 311121, P.R. China.
AD  - NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, 
      Hangzhou 310058, P.R. China.
AD  - Department of Neurobiology and Department of Orthopedics, 2nd Affiliated 
      Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 
      310003, P.R. China.
FAU - Li, Xiaodan
AU  - Li X
AD  - Liangzhu Laboratory, MOE Frontier Science Center for Brain Science and 
      Brain-Machine Integration, State Key Laboratory of Brain-Machine Intelligence, 
      Zhejiang University, 1369 West Wenyi Road, Hangzhou 311121, P.R. China.
AD  - NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, 
      Hangzhou 310058, P.R. China.
AD  - Department of Neurobiology and Department of Orthopedics, 2nd Affiliated 
      Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 
      310003, P.R. China.
FAU - Shen, Luoan
AU  - Shen L
AD  - Liangzhu Laboratory, MOE Frontier Science Center for Brain Science and 
      Brain-Machine Integration, State Key Laboratory of Brain-Machine Intelligence, 
      Zhejiang University, 1369 West Wenyi Road, Hangzhou 311121, P.R. China.
AD  - NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, 
      Hangzhou 310058, P.R. China.
FAU - Guo, Binjie
AU  - Guo B
AD  - Department of Neurobiology and Department of Rehabilitation Medicine, First 
      Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 
      Province 310003, P.R. China.
AD  - Liangzhu Laboratory, MOE Frontier Science Center for Brain Science and 
      Brain-Machine Integration, State Key Laboratory of Brain-Machine Intelligence, 
      Zhejiang University, 1369 West Wenyi Road, Hangzhou 311121, P.R. China.
AD  - NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, 
      Hangzhou 310058, P.R. China.
FAU - Abdelrahman, Zeinab
AU  - Abdelrahman Z
AD  - Department of Neurobiology and Department of Rehabilitation Medicine, First 
      Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 
      Province 310003, P.R. China.
AD  - Liangzhu Laboratory, MOE Frontier Science Center for Brain Science and 
      Brain-Machine Integration, State Key Laboratory of Brain-Machine Intelligence, 
      Zhejiang University, 1369 West Wenyi Road, Hangzhou 311121, P.R. China.
AD  - NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, 
      Hangzhou 310058, P.R. China.
AD  - Department of Neurobiology and Department of Orthopedics, 2nd Affiliated 
      Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 
      310003, P.R. China.
FAU - Zhou, Songlin
AU  - Zhou S
AD  - Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Nantong 
      University, Nantong, Jiangsu 226001, P.R. China.
FAU - Mao, Susu
AU  - Mao S
AD  - Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Nantong 
      University, Nantong, Jiangsu 226001, P.R. China.
FAU - Wang, Yaxian
AU  - Wang Y
AD  - Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Nantong 
      University, Nantong, Jiangsu 226001, P.R. China.
FAU - Yao, Chun
AU  - Yao C
AD  - Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Nantong 
      University, Nantong, Jiangsu 226001, P.R. China.
FAU - Gu, Xiaosong
AU  - Gu X
AD  - Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Nantong 
      University, Nantong, Jiangsu 226001, P.R. China.
FAU - Yu, Bin
AU  - Yu B
AD  - Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Nantong 
      University, Nantong, Jiangsu 226001, P.R. China.
FAU - Wang, Zhiping
AU  - Wang Z
AD  - Liangzhu Laboratory, MOE Frontier Science Center for Brain Science and 
      Brain-Machine Integration, State Key Laboratory of Brain-Machine Intelligence, 
      Zhejiang University, 1369 West Wenyi Road, Hangzhou 311121, P.R. China.
AD  - NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, 
      Hangzhou 310058, P.R. China.
AD  - Department of Neurobiology and Department of Orthopedics, 2nd Affiliated 
      Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 
      310003, P.R. China.
FAU - Wang, Xuhua
AU  - Wang X
AD  - Department of Neurobiology and Department of Rehabilitation Medicine, First 
      Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 
      Province 310003, P.R. China.
AD  - Liangzhu Laboratory, MOE Frontier Science Center for Brain Science and 
      Brain-Machine Integration, State Key Laboratory of Brain-Machine Intelligence, 
      Zhejiang University, 1369 West Wenyi Road, Hangzhou 311121, P.R. China.
AD  - NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, 
      Hangzhou 310058, P.R. China.
AD  - Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu 
      226001, P.R. China.
AD  - Department of Neurobiology and Department of Orthopedics, 2nd Affiliated 
      Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 
      310003, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20221226
PL  - United States
TA  - iScience
JT  - iScience
JID - 101724038
PMC - PMC9840934
OTO - NOTNLM
OT  - Biological sciences
OT  - Molecular neuroscience
OT  - Neuroscience
COIS- Zhejiang University has filed a patent application related to this work, with 
      X.W. listed as an inventor. X.W. is a scientific co-founder of WeQure AI Ltd. All 
      the other authors declare no conflicting interests.
EDAT- 2023/01/20 06:00
MHDA- 2023/01/20 06:01
PMCR- 2022/12/26
CRDT- 2023/01/19 01:58
PHST- 2022/06/23 00:00 [received]
PHST- 2022/10/27 00:00 [revised]
PHST- 2022/12/23 00:00 [accepted]
PHST- 2023/01/19 01:58 [entrez]
PHST- 2023/01/20 06:00 [pubmed]
PHST- 2023/01/20 06:01 [medline]
PHST- 2022/12/26 00:00 [pmc-release]
AID - S2589-0042(22)02158-7 [pii]
AID - 105885 [pii]
AID - 10.1016/j.isci.2022.105885 [doi]
PST - epublish
SO  - iScience. 2022 Dec 26;26(1):105885. doi: 10.1016/j.isci.2022.105885. eCollection 
      2023 Jan 20.