冷历歌
教授，教育部长江学者-青年学者，厦门大学南强拔尖人才，博士生导师
研究方向：神经退行性疾病的致病机制
所在系部：神经科学研究所
办公电话：0592-2180526
邮 箱：lenglige@xmu.edu.cn
研究领域
本课题组致力于阿尔茨海默病、衰老等的致病机制研究，近期在Nature Metabolism，Neuron，Cell Reports，PLOS Biology，Advanced Science等国际学术期刊上发表系列研究论文，系统解析了这类疾病的分子机制与治疗靶点。课题组利用基因修饰、电生理、动物行为学、多组学分析等相关技术，以疾病动物模型为研究对象，深入阐明阿尔茨海默病的致病机制，为临床早期诊断和靶向药物的开发提供模型和理论依据。除此之外，本课题组还进行精神情绪疾病如抑郁症、自闭症的发病机制的研究。主要方向包括：
1. 小胶质细胞代谢模式转换在AD致病中的作用及机制研究；
2. 压力应激下星形胶质细胞代谢异常及其对全身的代谢调控；
3. 下丘脑的能量代谢改变与衰老的相互关系；
4. AD早期诊断标志物和靶向药物的筛选。
学习经历
2010~2013 首都医科大学/北京市神经外科研究所 神经外科 医学博士；
2003~2010 首都医科大学 七年制本硕连读临床医学专业/外科学专业 医学学士/医学硕士；
工作经历
2023.9~至今 厦门大学医学院 教授
2019.8~2023.8 厦门大学医学院 副教授；
2016.1~2019.7 厦门大学医学院 助理教授；
2013.9~2015.12 第二军医大学/全军神经外科中心，中国人民解放军海军总医院神经外科 博士后。
代表性成果
1. Lige Leng*; Ziqi Yuan; Ruiyuan Pan; Xiao Su; Han Wang; Jin Xue; Kai Zhuang; Ju Gao; Zhenlei Chen; Hui Lin; Wenting Xie; Huifang Li; Zhenyi Chen; Keke Ren; Xiao Zhang; Wenting Wang;Zi-Bing Jin; Shengxi Wu; Xinglong Wang; Zengqiang Yuan; Huaxi Xu; Hei-Man Chow; Jie Zhang*; Microglial hexokinase 2 deficiency increases ATP generation through lipid metabolism leading to β-amyloid clearance, Nature Metabolism, 2022, 4(10): 1287-1305
2. Leng Lige; Zhuang Kai; Liu Zeyue; Huang Changquan; Gao Yuehong; Chen Guimiao; Lin Hui; Hu Yu; Wu Di; Shi Meng; Xie Wenting; Sun Hao; Shao Zhicheng; Li Huifang; Zhang Kunkun; Mo Wei; Huang Timothy Y; Xue Maoqiang; Yuan Zengqiang; Zhang Xia; Bu Guojun; Xu Huaxi; Xu Qi*; Zhang Jie*; Menin Deficiency Leads to Depressive-like Behaviors in Mice by Modulating Astrocyte-Mediated Neuroinflammation, Neuron, 2018, 100(3): 1-13
3. Lige Leng*; Ziqi Yuan; Xiao Su; Zhenlei Chen; Shangchen Yang; Meiqin Chen; Kai Zhuang; HuiLin; Hao Sun; Huifang Li; Maoqiang Xue; Jun Xu; Jingqi Yan; Zhenyi Chen; Tifei Yuan; Jie Zhang*; Hypothalamic Menin regulates systemic aging and cognitive decline, Plos Biology, 2023, 21(3): e3002033
4. Leng L*, Zhuang K, Lin H, Ding J, Yang S, Yuan Z, Huang C, Chen G, Chen Z, Wang M, Wang H, Sun H, Li H, Chang H, Chen Z, Xu Q, Yuan T, Zhang J*. Menin Reduces Parvalbumin Expression and is Required for the Anti-Depressant Function of Ketamine. Adv Sci (Weinh). 2023 Dec 3:e2305659. doi: 10.1002/advs.202305659.
5. Shangchen Yang#, Ziqi Yuan#, Yufei Zhu#, Chensi Liang, Zhenlei Chen, Jie Zhang*, Lige Leng*, Multi-omics analysis reveals GAPDH posttranscriptional regulation of IFN-γ and PHGDH as a metabolic checkpoint of microglia polarization. Brain Behav Immun. 2024 Jan 11;117:155-166. doi: 10.1016/j.bbi.2024.01.009.
6. Zhuang Kai#; Huang Changquan#; Leng Lige#; Zheng Honghua#; Gao Yuehong#; Chen Guimiao; Ji Zhilin; Sun Hao; Hu Yu; Wu Di; Shi Meng; Li Huifang; Zhao Yingjun; Zhang Yunwu; Xue Maoqiang; Bu Guojun; Huang Timothy Y; Xu Huaxi; Zhang Jie*; Neuron-Specific Menin Deletion Leads to Synaptic Dysfunction and Cognitive Impairment by Modulating p35 Expression, Cell Reports, 2018, 24(3):701-712
7. Zhenlei Chen; Ziqi Yuan; Shangchen Yang; Yufei Zhu; Maoqiang Xue; Jie Zhang*; Lige Leng*; Brain Energy Metabolism: Astrocytes in Neurodegenerative Diseases, CNS Neuroscience &Therapeutics, 2022, 29(1): 24-36
8. Yuan Ziqi; Chen Zhenlei; Xue Maoqiang; Zhang Jie*; Leng Lige*; Application of antidepressants in depression: A systematic review and meta-analysis, Journal of Clinical Neuroscience, 2020, 80: 169-181
承担的重要课题
1. 国家自然科学基金委员会, 面上项目, 82371566，下丘脑Menin缺失导致系统性衰老和认知障碍的机制研究，2024-01-01 至 2027-12-31, 49万元, 在研, 主持
2. 国家自然科学基金委员会, 面上项目, 82071520, Men1突变（G503D）以及Men1缺失导致中间神经元功能紊乱在抑郁发生发展中的作用机制研究, 2021-01-01 至 2024-12-31, 55万元, 在研, 主持
3. 国家自然科学基金委员会, 联合基金项目, U1905207, CDK3调控阿尔茨海默病中神经元死亡的机制及干预研究, 2020-01-01 至 2023-12-31, 227万元, 在研, 参与
4. 国家自然科学基金委员会, 重大研究计划, 91849205, 胰岛素抵抗导致神经元衰老的分子机制及在老年痴呆疾病中的作用研究, 2019-01-01 至 2022-12-31, 200万元, 结题, 参与
5. 国家自然科学基金委员会, 青年科学基金项目, 81801337, 星形胶质细胞中缺失menin导致抑郁的发生及其作用机制的研究, 2019-01-01 至 2021-12-31, 23万元, 结题, 主持
6. 厦门大学南强青年拔尖人才项目，2020-04-01至2025-07-01，75万元，在研，主持
7. 中央高校建设经费（校长基金），2023-01-01 至 2025-12-31, 70万元, 在研, 主持
获奖及荣誉
1. 教育部长江学者-青年学者，2023年；
2. 福建省自然科学优秀学术论文二等奖，2020年
3. 福建省首届解剖学教学比赛二等奖，第二届教学比赛三等奖，2021年，2023年；
4. 中国解剖学会首届日升隆杯教学比赛三等奖，2023年。
所有论文列表
1. Leng L*, Yuan Z, Pan R, Su X, Wang H, Xue J, Zhuang K, Gao J, Chen Z, Lin H, Xie W, Li H, Chen Z, Ren K, Zhang X, Wang W, Jin ZB, Wu S, Wang X, Yuan Z, Xu H, Chow HM, Zhang J*. Microglial hexokinase 2 deficiency increases ATP generation through lipid metabolism leading to β-amyloid clearance. Nat Metab. 2022 Oct;4(10):1287-1305. doi: 10.1038/s42255-022-00643-4. Epub 2022 Oct 6. Erratum in: Nat Metab. 2022 Oct 14;: PMID: 36203054.
2. Leng L, Zhuang K, Liu Z, Huang C, Gao Y, Chen G, Lin H, Hu Y, Wu D, Shi M, Xie W, Sun H, Shao Z, Li H, Zhang K, Mo W, Huang TY, Xue M, Yuan Z, Zhang X, Bu G, Xu H, Xu Q, Zhang J*. Menin Deficiency Leads to Depressive-like Behaviors in Mice by Modulating Astrocyte-Mediated Neuroinflammation. Neuron. 2018 Nov 7;100(3):551-563.e7. doi: 10.1016/j.neuron.2018.08.031. Epub 2018 Sep 13. PMID: 30220511.
3. Chen Z, Yuan Z, Yang S, Zhu Y, Xue M, Zhang J*, Leng L*. Brain Energy Metabolism: Astrocytes in Neurodegenerative Diseases. CNS Neurosci Ther. 2023 Jan;29(1):24-36. doi: 10.1111/cns.13982. Epub 2022 Oct 3. PMID: 36193573; PMCID: PMC9804080.
4. Leng L*, Zhuang K, Lin H, Ding J, Yang S, Yuan Z, Huang C, Chen G, Chen Z, Wang M, Wang H, Sun H, Li H, Chang H, Chen Z, Xu Q, Yuan T, Zhang J*. Menin Reduces Parvalbumin Expression and is Required for the Anti-Depressant Function of Ketamine. Adv Sci (Weinh). 2023 Dec 3:e2305659. doi: 10.1002/advs.202305659.
5. Shangchen Yang#, Ziqi Yuan#, Yufei Zhu#, Chensi Liang, Zhenlei Chen, Jie Zhang*, Lige Leng*, Multi-omics analysis reveals GAPDH posttranscriptional regulation of IFN-γ and PHGDH as a metabolic checkpoint of microglia polarization. Brain Behav Immun. 2024 Jan 11;117:155-166. doi: 10.1016/j.bbi.2024.01.009.
6. Leng L*, Yuan Z, Su X, Chen Z, Yang S, Chen M, Zhuang K, Lin H, Sun H, Li H, Xue M, Xu J, Yan J, Chen Z, Yuan T, Zhang J*. Hypothalamic Menin regulates systemic aging and cognitive decline. PLoS Biol. 2023 Mar 16;21(3):e3002033. doi: 10.1371/journal.pbio.3002033. PMID: 36928253; PMCID: PMC10019680.
7. Xie W, Guo D, Li J, Yue L, Kang Q, Chen G, Zhou T, Wang H, Zhuang K, Leng L, Li H, Chen Z, Gao W, Zhang J*. CEND1 deficiency induces mitochondrial dysfunction and cognitive impairment in Alzheimer's disease. Cell Death Differ. 2022 Dec;29(12):2417-2428. doi: 10.1038/s41418-022-01027-7. Epub 2022 Jun 22. PMID: 35732922; PMCID: PMC9751129.
8. Yuan Z, Chen Z, Xue M, Zhang J*, Leng L*. Application of antidepressants in depression: A systematic review and meta-analysis. J Clin Neurosci. 2020 Oct;80:169-181. doi: 10.1016/j.jocn.2020.08.013. Epub 2020 Aug 19. PMID: 33099342.
9. Leng L*, Zhang J*. Microglial metabolic reconfiguration provides a new strategy for the treatment of Alzheimer's disease. Neural Regen Res. 2023 Sep;18(9):1946-1947. doi: 10.4103/1673-5374.367842. PMID: 36926714; PMCID: PMC10233783.
10.Zhou J, Chow HM, Liu Y, Wu D, Shi M, Li J, Wen L, Gao Y, Chen G, Zhuang K, Lin H, Zhang G, Xie W, Li H, Leng L, Wang M, Zheng N, Sun H, Zhao Y, Zhang Y, Xue M, Huang TY, Bu G, Xu H, Yuan Z, Herrup K, Zhang J*. Cyclin-Dependent Kinase 5-Dependent BAG3 Degradation Modulates Synaptic Protein Turnover. Biol Psychiatry. 2020 Apr 15;87(8):756-769. doi: 10.1016/j.biopsych.2019.11.013. Epub 2019 Nov 21. PMID: 31955914.
11.Tian CY, Leng LG, Tian ZM*. [How to deal with cerebral palsy in 21st century--a new epoch in clinic treatment]. Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2014 Nov;30(6):511-5. Chinese. PMID: 26016360.
12.Leng L, Zhang Y*. Etiology of Pituitary Tumors: A Case Control Study. Turk Neurosurg. 2016;26(2):195-9. doi: 10.5137/1019-5149.JTN.5985-12.1. PMID: 26956811.
13.Zhuang K, Huang C, Leng L, Zheng H, Gao Y, Chen G, Ji Z, Sun H, Hu Y, Wu D, Shi M, Li H, Zhao Y, Zhang Y, Xue M, Bu G, Huang TY, Xu H, Zhang J*. Neuron-Specific Menin Deletion Leads to Synaptic Dysfunction and Cognitive Impairment by Modulating p35 Expression. Cell Rep. 2018 Jul 17;24(3):701-712. doi: 10.1016/j.celrep.2018.06.055. PMID: 30021166; PMCID: PMC6434950.
14.Leng L*. Hypothermia Therapy after Traumatic Brain Injury: A Systematic Review and Meta-Analysis. Turk Neurosurg. 2017 Oct 29. doi: 10.5137/1019-5149.JTN.19696-16.2. Epub ahead of print. PMID: 29165744.
15.Leng L, Jiang T*, Zhang Y*. TLR9 expression is associated with prognosis in patients with glioblastoma multiforme. J Clin Neurosci. 2012 Jan;19(1):75-80. doi: 10.1016/j.jocn.2011.03.037. Epub 2011 Dec 9. PMID: 22169598.
16.Leng L, Zhang Y*. Effects of an estrogen receptor antagonist on proliferation, prolactin secretion and growth factor expression in the MMQ pituitary prolactinoma cell line. J Clin Neurosci. 2011 Dec;18(12):1694-8. doi: 10.1016/j.jocn.2011.06.013. Epub 2011 Oct 19. PMID: 22015101.
17.Lige L, Zengmin T*. Transplantation of Neural Precursor Cells in the Treatment of Parkinson Disease: An Efficacy and Safety Analysis. Turk Neurosurg. 2016;26(3):378-83. doi: 10.5137/1019-5149.JTN.10747-14.4. PMID: 27161464.
