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NAD+ rescues aging-induced blood-brain barrier damage via the CX43-PARP1 axis.
Zhan, Rui; Meng, Xia; Tian, Dongping; Xu, Jie; Cui, Hongtu; Yang, Jialei; Xu, Yangkai; Shi, Mingming; Xue, Jing; Yu, Weiwei; Hu, Gaofei; Li, Ke; Ge, Xiaoxiao; Zhang, Qi; Zhao, Mingming; Du, Jianyong; Guo, Xin; Xu, Wenli; Gao, Yang; Yao, Changyu; Chen, Fan; Chen, Yue; Shan, Wenxin; Zhu, Yujie; Ji, Liang; Pan, Bing; Yu, Yan; Li, Wenguang; Zhao, Xuyang; He, Qihua; Liu, Xiaohui; Huang, Yue; Liao, Shengyou; Zhou, Bin; Chui, Dehua; Chen, Y Eugene; Sun, Zheng; Dong, Erdan; Wang, Yongjun; Zheng, Lemin.
Afiliación
  • Zhan R; The Institute of Cardiovascular Sciences, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Receptors Research, Health Science Center,
  • Meng X; Beijing Tiantan Hospital, China National Clinical Research Center for Neurological Diseases, Advanced Innovation Center for Human Brain Protection, The Capital Medical University, Beijing, China.
  • Tian D; Department of Pathology, Medical College, Shantou University, Shantou, China.
  • Xu J; Beijing Tiantan Hospital, China National Clinical Research Center for Neurological Diseases, Advanced Innovation Center for Human Brain Protection, The Capital Medical University, Beijing, China.
  • Cui H; Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Beijing, China.
  • Yang J; Beijing Tiantan Hospital, China National Clinical Research Center for Neurological Diseases, Advanced Innovation Center for Human Brain Protection, The Capital Medical University, Beijing, China.
  • Xu Y; The Institute of Cardiovascular Sciences, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Receptors Research, Health Science Center,
  • Shi M; Beijing Tiantan Hospital, China National Clinical Research Center for Neurological Diseases, Advanced Innovation Center for Human Brain Protection, The Capital Medical University, Beijing, China.
  • Xue J; Beijing Tiantan Hospital, China National Clinical Research Center for Neurological Diseases, Advanced Innovation Center for Human Brain Protection, The Capital Medical University, Beijing, China.
  • Yu W; Peking University Shenzhen Hospital, Beijing, China.
  • Hu G; The Institute of Cardiovascular Sciences, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Receptors Research, Health Science Center,
  • Li K; Beijing Tiantan Hospital, China National Clinical Research Center for Neurological Diseases, Advanced Innovation Center for Human Brain Protection, The Capital Medical University, Beijing, China.
  • Ge X; Beijing Institute Brain Disorders, Capital Medical University, Beijing, China.
  • Zhang Q; The Institute of Cardiovascular Sciences, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Receptors Research, Health Science Center,
  • Zhao M; Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Beijing, China.
  • Du J; Research Center for Cardiopulmonary Rehabilitation, University of Health and Rehabilitation Sciences Qingdao Hospital (Qingdao Municipal Hospital), School of Health and Life Sciences, University of Health and Rehabilitation Sciences, Qingdao 266071, China.
  • Guo X; Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Beijing, China.
  • Xu W; Research Center for Cardiopulmonary Rehabilitation, University of Health and Rehabilitation Sciences Qingdao Hospital (Qingdao Municipal Hospital), School of Health and Life Sciences, University of Health and Rehabilitation Sciences, Qingdao 266071, China.
  • Gao Y; Research Center for Cardiopulmonary Rehabilitation, University of Health and Rehabilitation Sciences Qingdao Hospital (Qingdao Municipal Hospital), School of Health and Life Sciences, University of Health and Rehabilitation Sciences, Qingdao 266071, China.
  • Yao C; Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
  • Chen F; Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.
  • Chen Y; The Institute of Cardiovascular Sciences, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Receptors Research, Health Science Center,
  • Shan W; The Institute of Cardiovascular Sciences, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Receptors Research, Health Science Center,
  • Zhu Y; The Institute of Cardiovascular Sciences, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Receptors Research, Health Science Center,
  • Ji L; The Institute of Cardiovascular Sciences, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Receptors Research, Health Science Center,
  • Pan B; The Institute of Cardiovascular Sciences, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Receptors Research, Health Science Center,
  • Yu Y; Chinese Institute of Rehabilitation Science, China Rehabilitation Research Center, Beijing Key Laboratory of Neural Injury and Rehabilitation, Beijing, China.
  • Li W; Institute of Genetics and Development Biology, Chinese Academy of Sciences, Beijing, China.
  • Zhao X; The Institute of Cardiovascular Sciences, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Receptors Research, Health Science Center,
  • He Q; Center of Medical and Health Analysis, Peking University, Beijing, China.
  • Liu X; National Protein Science Technology Center, Tsinghua University, Beijing, China.
  • Huang Y; Beijing Tiantan Hospital, China National Clinical Research Center for Neurological Diseases, Advanced Innovation Center for Human Brain Protection, The Capital Medical University, Beijing, China.
  • Liao S; Department of Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, The Second Clinical Medical College, Jinan University, Shenzhen People's Hospital, Shenzhen, China.
  • Zhou B; State Key Laboratory of Cell Biology, Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
  • Chui D; Beijing Key Laboratory of Magnetic Resonance Imaging Devices and Technology and Department of Neurology, Peking University Third Hospital, Beijing, China.
  • Chen YE; Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, MI, USA.
  • Sun Z; Department of Medicine and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
  • Dong E; The Institute of Cardiovascular Sciences, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Receptors Research, Health Science Center,
  • Wang Y; Beijing Tiantan Hospital, China National Clinical Research Center for Neurological Diseases, Advanced Innovation Center for Human Brain Protection, The Capital Medical University, Beijing, China. Electronic address: yongjunwang@ncrcnd.org.cn.
  • Zheng L; The Institute of Cardiovascular Sciences, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Receptors Research, Health Science Center,
Neuron ; 111(22): 3634-3649.e7, 2023 11 15.
Article en En | MEDLINE | ID: mdl-37683629
ABSTRACT
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.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Conexina 43 / NAD Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Neuron Asunto de la revista: NEUROLOGIA Año: 2023 Tipo del documento: Article
Texto completo
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Conexina 43 / NAD Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Neuron Asunto de la revista: NEUROLOGIA Año: 2023 Tipo del documento: Article