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NAD+ rescues aging-induced blood-brain barrier damage via the CX43-PARP1 axis

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收录情况： ◇ SCIE ◇ 自然指数

作者：
Rui Zhan[1,2] * ; Xia Meng[3] * ; Dongping Tian[4] ; Jie Xu[3] ; Hongtu Cui[5] ; Jialei Yang[3] ; Yangkai Xu[1] ; Mingming Shi[3] ; Jing Xue[3] ; Weiwei Yu[6] ; Gaofei Hu[1] ; Ke Li Xiaoxiao Ge[3,7] ; Qi Zhang[1] ; Mingming Zhao[5] ; Jianyong Du[2] ; Xin Guo[5] ; Wenli Xu[2] ; Yang Gao[2] ; Changyu Yao[8] ; Fan Chen[9] ; Yue Chen[1] ; Wenxin Shan[1] ; Yujie Zhu[1] ; Liang Ji[1] ; Bing Pan[1] ; Yan Yu[10] ; Wenguang Li[11] ; Xuyang Zhao[1] ; Qihua He[12] ; Xiaohui Liu[13] ; Yue Huang[3] ; Shengyou Liao[14] ; Bin Zhou[15] ; Dehua Chui[16] ; Y. Eugene Chen[17] ; Zheng Sun[18] ; Erdan Dong[1,2,5,19] ; Yongjun Wang[3] ; Lemin Zheng[1,3] ;
机构： [1]The Institute of Cardiovascular Sciences, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis andRemodeling, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of CardiovascularReceptors Research, Health Science Center, Peking University, Beijing 100191, China [2]Research Center for Cardiopulmonary Rehabilitation, University of Health and Rehabilitation Sciences Qingdao Hospital (Qingdao MunicipalHospital), School of Health and Life Sciences, University of Health and Rehabilitation Sciences, Qingdao 266071, China [3]Beijing Tiantan Hospital, China National Clinical Research Center for Neurological Diseases, Advanced Innovation Center for Human BrainProtection, The Capital Medical University, Beijing, China [4]Department of Pathology, Medical College, Shantou University, Shantou, China [5]Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Beijing, China [6]Peking University Shenzhen Hospital, Beijing, China [7]Beijing Institute Brain Disorders, Capital Medical University, Beijing, China [8]Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China [9]Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China [10]Chinese Institute of Rehabilitation Science, China Rehabilitation Research Center, Beijing Key Laboratory of Neural Injury andRehabilitation, Beijing, China [11]Institute of Genetics and Development Biology, Chinese Academy of Sciences, Beijing, China [12]Center of Medical and Health Analysis, Peking University, Beijing, China [13]National Protein Science Technology Center, Tsinghua University, Beijing, China [14]Department of Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease PrecisionMedicine, The Second Clinical Medical College, Jinan University, Shenzhen People’s Hospital, Shenzhen, China [15]State Key Laboratory of Cell Biology, Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, Institute ofBiochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China [16]Beijing Key Laboratory of Magnetic Resonance Imaging Devices and Technology and Department of Neurology, Peking University ThirdHospital, Beijing, China [17]Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, MI, USA [18]Department of Medicine and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA [19]Research Unit of Medical Science Research Management/Basic and Clinical Research of Metabolic Cardiovascular Diseases, ChineseAcademy of Medical Sciences, Haihe Laboratory of Cell Ecosystem, Beijing, China [20]The Institute of Systems Biomedicine, School of Basic Medical Sciences, Health Science Center, Peking University, Beijing, China
出处：
DOI： 10.1016/j.neuron.2023.08.010
ISSN：

摘要：
Blood-brain barrier (BBB) function deteriorates during aging, contributing to cognitive impairment and neurodegeneration. It is unclear what drives BBB leakage in aging and how it can be prevented. Using single-nucleus transcriptomics, we identified decreased connexin 43 (CX43) expression in cadherin-5+ (Cdh5+) cerebral vascular cells in naturally aging mice and confirmed it in human brain samples. Global or Cdh5+ cell-specific CX43 deletion in mice exacerbated BBB dysfunction during aging. The CX43-dependent effect was not due to its canonical gap junction function but was associated with reduced NAD+ levels and mitochondrial dysfunction through NAD+-dependent sirtuin 3 (SIRT3). CX43 interacts with and negatively regulates poly(ADP-ribose) polymerase 1 (PARP1). Pharmacologic inhibition of PARP1 by olaparib or nicotinamide mononucleotide (NMN) supplementation rescued NAD+ levels and alleviated aging-associated BBB leakage. These findings establish the endothelial CX43-PARP1-NAD+ pathway's role in vascular aging and identify a potential therapeutic strategy to combat aging-associated BBB leakage with neuroprotective implications.Copyright © 2023 Elsevier Inc. All rights reserved.

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出版当年[2022]版：
大类 | 1 区 医学
小类 | 1 区 神经科学
最新[2023]版：
大类 | 1 区 医学
小类 | 1 区 神经科学
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Q1 NEUROSCIENCES
最新[2023]版：
Q1 NEUROSCIENCES

影响因子： 最新[2023版] 最新五年平均 出版当年[2021版] 出版当年五年平均 出版前一年[2020版] 出版后一年[2022版]

第一作者：
第一作者机构： [1]The Institute of Cardiovascular Sciences, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis andRemodeling, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of CardiovascularReceptors Research, Health Science Center, Peking University, Beijing 100191, China [2]Research Center for Cardiopulmonary Rehabilitation, University of Health and Rehabilitation Sciences Qingdao Hospital (Qingdao MunicipalHospital), School of Health and Life Sciences, University of Health and Rehabilitation Sciences, Qingdao 266071, China
共同第一作者：
通讯作者：
通讯机构： [1]The Institute of Cardiovascular Sciences, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis andRemodeling, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of CardiovascularReceptors Research, Health Science Center, Peking University, Beijing 100191, China [2]Research Center for Cardiopulmonary Rehabilitation, University of Health and Rehabilitation Sciences Qingdao Hospital (Qingdao MunicipalHospital), School of Health and Life Sciences, University of Health and Rehabilitation Sciences, Qingdao 266071, China [3]Beijing Tiantan Hospital, China National Clinical Research Center for Neurological Diseases, Advanced Innovation Center for Human BrainProtection, The Capital Medical University, Beijing, China [5]Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Beijing, China [19]Research Unit of Medical Science Research Management/Basic and Clinical Research of Metabolic Cardiovascular Diseases, ChineseAcademy of Medical Sciences, Haihe Laboratory of Cell Ecosystem, Beijing, China
推荐引用方式(GB/T 7714)：
Rui Zhan,Xia Meng,Dongping Tian,et al.NAD+ rescues aging-induced blood-brain barrier damage via the CX43-PARP1 axis[J].NEURON.2023,111(22):doi:10.1016/j.neuron.2023.08.010.
APA：
Rui Zhan,Xia Meng,Dongping Tian,Jie Xu,Hongtu Cui...&Lemin Zheng.(2023).NAD+ rescues aging-induced blood-brain barrier damage via the CX43-PARP1 axis.NEURON,111,(22)
MLA：
Rui Zhan,et al."NAD+ rescues aging-induced blood-brain barrier damage via the CX43-PARP1 axis".NEURON 111..22(2023)

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