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Deficiency in endocannabinoid synthase DAGLB contributes to early onset Parkinsonism and murine nigral dopaminergic neuron dysfunction.

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收录情况： ◇ SCIE ◇ 自然指数

作者：
Zhenhua Liu[1,2] * ; Nannan Yang[1,2] * ; Jie Dong[1,3] * ; Wotu Tian[1,4] ; Lisa Chang[1] ; Jinghong Ma[5] ; Jifeng Guo[2] ; Jieqiong Tan[6] ; Ao Dong [7,8,9] ; Kaikai He[7,8] ; Jingheng Zhou[10] ; Resat Cinar[11] ; Junbing Wu[1] ; Armando G. Salinas[12] ; Lixin Sun[1] ; Mantosh Kumar[1] ; Breanna T. Sullivan[1] ; Braden B. Oldham[1] ; Vanessa Pitz[13] ; Mary B. Makarious[13] ; Jinhui Ding[14] ; Justin Kung[1] ; Chengsong Xie[1] ; Sarah L. Hawes[1] ; Lupeng Wang[1] ; Tao Wang[15] ; Piu Chan[5] ; Zhuohua Zhang[6,16] ; Weidong Le[3,17] ; Shengdi Chen[4] ; David M. Lovinger[12] ; Cornelis Blauwendraat[18] ; Andrew B. Singleton[13,19] ; Guohong Cui[10] ; Yulong Li[7,8,9,20] ; Huaibin Cai[1,24] ; Beisha Tang[2,6,21,22] ;
机构： [1]Transgenic Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA [2]Department of Neurology, Xiangya Hospital, Central South University, 410008 Changsha, Hunan, China [3]Clinical Research Center onNeurological Diseases, the First Affiliated Hospital, Dalian Medical University, 116011 Dalian, Liaoning, China [4]Department of Neurology, RuijinHospital Affiliated to Shanghai Jiao Tong University School of Medicine, 20025 Shanghai, China [5]Department of Neurology, Xuanwu Hospital ofCapital Medical University, 100053 Beijing, China [6]Centre for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of LifeSciences, Central South University, 410008 Changsha, Hunan, China [7]State Key Laboratory of Membrane Biology, Peking University School ofLife Sciences, 100871 Beijing, China [8]PKU-IDG/McGovern Institute for Brain Research, 100871 Beijing, China [9]Peking-Tsinghua Center for LifeSciences, Academy for Advanced Interdisciplinary Studies, Peking University, 100871 Beijing, China [10]In Vivo Neurobiology Group, NeurobiologyLaboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA [11]Laboratory of Physiologic Studies,National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA [12]Laboratory for IntegrativeNeuroscience, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD 20852, USA [13]MolecularGenetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA [14]Computational Biology Group, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892,USA [15]Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022 Wuhan,Hubei, China [16]Department of Neurosciences, University of South China Medical School, 421200 Hengyang, Hunan, China [17]Institute ofNeurology, Sichuan Academy of Medical Sciences-Sichuan Provincial Hospital, Medical School of University of Electronics & Technology ofChina, 610045 Chengdu, Sichuan, China [18]Integrative Neurogenomics Unit, Laboratory of Neurogenetics, National Institute on Aging, NationalInstitutes of Health, Bethesda, MD 20892, USA [19]Center for Alzheimer’s and Related Dementias, National Institutes of Health, Bethesda, MD20892, USA [20]Chinese Institute for Brain Research, 102206 Beijing, China [21]National Clinical Research Center for Geriatric Disorders, XiangyaHospital, Central South University, 410008 Changsha, Hunan, China [22]Key Laboratory of Hunan Province in Neurodegenerative Disorders,Central South University, 410008 Changsha, Hunan, China
出处：
DOI： 10.1038/s41467-022-31168-9
ISSN：

摘要：
Endocannabinoid (eCB), 2-arachidonoyl-glycerol (2-AG), the most abundant eCB in the brain, regulates diverse neural functions. Here we linked multiple homozygous loss-of-function mutations in 2-AG synthase diacylglycerol lipase β (DAGLB) to an early onset autosomal recessive Parkinsonism. DAGLB is the main 2-AG synthase in human and mouse substantia nigra (SN) dopaminergic neurons (DANs). In mice, the SN 2-AG levels were markedly correlated with motor performance during locomotor skill acquisition. Genetic knockdown of Daglb in nigral DANs substantially reduced SN 2-AG levels and impaired locomotor skill learning, particularly the across-session learning. Conversely, pharmacological inhibition of 2-AG degradation increased nigral 2-AG levels, DAN activity and dopamine release and rescued the locomotor skill learning deficits. Together, we demonstrate that DAGLB-deficiency contributes to the pathogenesis of Parkinsonism, reveal the importance of DAGLB-mediated 2-AG biosynthesis in nigral DANs in regulating neuronal activity and dopamine release, and suggest potential benefits of 2-AG augmentation in alleviating Parkinsonism.© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.

基金：
National Institutes of Health (NIH).
语种：
外文
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出版当年[2021]版：
大类 | 1 区 综合性期刊
小类 | 1 区 综合性期刊
最新[2025]版：
大类 | 1 区 综合性期刊
小类 | 1 区 综合性期刊
JCR分区：
出版当年[2020]版：
Q1 MULTIDISCIPLINARY SCIENCES
最新[2024]版：
Q1 MULTIDISCIPLINARY SCIENCES

影响因子： 最新[2024版] 最新五年平均 出版当年[2020版] 出版当年五年平均 出版前一年[2019版] 出版后一年[2021版]

第一作者：
第一作者机构： [1]Transgenic Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA [2]Department of Neurology, Xiangya Hospital, Central South University, 410008 Changsha, Hunan, China
共同第一作者：
通讯作者：
通讯机构： [1]Transgenic Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA [2]Department of Neurology, Xiangya Hospital, Central South University, 410008 Changsha, Hunan, China [6]Centre for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of LifeSciences, Central South University, 410008 Changsha, Hunan, China [21]National Clinical Research Center for Geriatric Disorders, XiangyaHospital, Central South University, 410008 Changsha, Hunan, China [22]Key Laboratory of Hunan Province in Neurodegenerative Disorders,Central South University, 410008 Changsha, Hunan, China
推荐引用方式(GB/T 7714)：
Zhenhua Liu,Nannan Yang,Jie Dong,et al.Deficiency in endocannabinoid synthase DAGLB contributes to early onset Parkinsonism and murine nigral dopaminergic neuron dysfunction.[J].NATURE COMMUNICATIONS.2022,13(1):doi:10.1038/s41467-022-31168-9.
APA：
Zhenhua Liu,Nannan Yang,Jie Dong,Wotu Tian,Lisa Chang...&Beisha Tang.(2022).Deficiency in endocannabinoid synthase DAGLB contributes to early onset Parkinsonism and murine nigral dopaminergic neuron dysfunction..NATURE COMMUNICATIONS,13,(1)
MLA：
Zhenhua Liu,et al."Deficiency in endocannabinoid synthase DAGLB contributes to early onset Parkinsonism and murine nigral dopaminergic neuron dysfunction.".NATURE COMMUNICATIONS 13..1(2022)

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