李靓 教授

主要研究方向

1.老年性神经退行性疾病发病机制研究

老年性神经退行性疾病主要包括帕金森病（PD）和阿尔茨海默病(AD)。PD是多巴胺（DA）神经元的丢失导致运动能力衰退，本课题组主要研究胶质细胞在PD发病过程中对DA神经元的作用机制。AD是一种中枢神经系统变性病,起病隐袭,病程呈慢性进行性,是老年期痴呆最常见的一种类型。AD病理目前的假说是淀粉样肽和tau蛋白沉积，但是目前针对淀粉样肽的药物开发并不理想，近年来最新的研究显示，小胶质细胞介导的突触清除异常是AD临床认知记忆功能衰退的关键，本课题组主要研究小胶质细胞突触清除的调控机制及干预，寻找治疗AD的潜在药物。

2.神经胶质瘤发病机制及干预研究

神经胶质瘤是是最常见的原发性中枢神经系统肿瘤，在胶质瘤周围存在大量的小胶质细胞（microglia）和巨噬细胞（macrophage）称为GAMM，上述细胞在生理状态下具有很强的吞噬能力，但是在肿瘤周围其能力变弱，本课题组主要研究如何调节干预GAMM的功能，利用肿瘤免疫的原理提高GAMM对肿瘤细胞的吞噬，减缓肿瘤的发生发展。

技术平台介绍

目前课题组成熟的技术平台包含原代胶质/神经细胞培养及功能分析，原代神经干细胞培养及功能分析，PD和AD小鼠模型建立和表型分析，神经元3D重构成像等，希望和有志向的学生一起做感兴趣的研究。

2012-至今，中国神经科学学会会员

FEBS J，Journal of Neuroinflammation，Neurobiology of Aging等杂志审稿专家

代表性研究论文：

Neuroprotective effects of (-)-epigallocatechin-3-gallate in a transgenic mouse model of amyotrophic lateral sclerosis.

Xu Z, Chen S, Li X, Luo G, Li L, Le W.

Neurochem Res. 2006 Oct;31(10):1263-9. Epub 2006 Oct 5.

Proteasome inhibitor lactacystin disturbs the intracellular calcium homeostasis of dopamine neurons in ventral mesencephalic cultures.

Li X, Yang D, Li L, Peng C, Chen S, Le W.

Neurochem Int. 2007 Jun;50(7-8):959-65. Epub 2007 May 3.

Glial cell-derived neurotrophic factor protects against proteasome inhibition-induced dopamine neuron degeneration by suppression of endoplasmic reticulum stress and caspase-3 activation.

Li X, Peng C, Li L, Ming M, Yang D, Le W.

J Gerontol A Biol Sci Med Sci. 2007 Sep;62(9):943-50.

Hypoxia increases Abeta generation by altering beta- and gamma-cleavage of APP.

Li L, Zhang X, Yang D, Luo G, Chen S, Le W.

Neurobiol Aging. 2009 Jul;30(7):1091-8. Epub 2007 Dec 11.

Altered macroautophagy in the spinal cord of SOD1 mutant mice.

Li L, Zhang X, Le W.

Autophagy. 2008 Apr;4(3):290-3. Epub 2008 Jan 7.

D2/D3 receptor agonist ropinirole protects dopaminergic cell line against rotenone-induced apoptosis through inhibition of caspase- and JNK-dependent pathways.

Chen S, Zhang X, Yang D, Du Y, Li L, Li X, Ming M, Le W.

FEBS Lett. 2008 Mar 5;582(5):603-10. doi: 10.1016/j.febslet.2008.01.028. Epub 2008 Jan 31.

Folic acid protects motor neurons against the increased homocysteine, inflammation and apoptosis in SOD1 G93A transgenic mice.

Zhang X, Chen S, Li L, Wang Q, Le W.

Neuropharmacology. 2008 Jun;54(7):1112-9. doi: 10.1016/j.neuropharm.2008.02.020. Epub 2008 Mar 16.

Current experimental therapy for Alzheimer's disease.

Chen S, Zhang XJ, Li L, Le WD.

Curr Neuropharmacol. 2007;5(2):127-34.

Pitx3-transfected astrocytes secrete brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor and protect dopamine neurons in mesencephalon cultures.

Yang D, Peng C, Li X, Fan X, Li L, Ming M, Chen S, Le W.

J Neurosci Res. 2008 Nov 15;86(15):3393-400. doi: 10.1002/jnr.21774.

Nurr1 expression and its modulation in microglia.

Fan X, Luo G, Ming M, Pu P, Li L, Yang D, Le W.

Neuroimmunomodulation. 2009;16(3):162-70. doi: 10.1159/000204229. Epub 2009 Feb 24.

An insight into the mechanistic role of p53-mediated autophagy induction in response to proteasomal inhibition-induced neurotoxicity.

Du Y, Yang D, Li L, Luo G, Li T, Fan X, Wang Q, Zhang X, Wang Y, Le W.

Autophagy. 2009 Jul;5(5):663-75.

Retinal pigment epithelial cells secrete neurotrophic factors and synthesize dopamine: possible contribution to therapeutic effects of RPE cell transplantation in Parkinson's disease.

Ming M, Li X, Fan X, Yang D, Li L, Chen S, Gu Q, Le W.

J Transl Med. 2009 Jun 28;7:53. doi: 10.1186/1479-5876-7-53.

Decreased level of 5-methyltetrahydrofolate: a potential biomarker for pre-symptomatic amyotrophic lateral sclerosis.

Zhang X, Chen S, Li L, Wang Q, Le W.

J Neurol Sci. 2010 Jun 15;293(1-2):102-5. doi: 10.1016/j.jns.2010.02.024. Epub 2010 Mar 23.

Autophagy dysfunction in Alzheimer's disease.

Li L, Zhang X, Le W.

Neurodegener Dis. 2010;7(4):265-71. doi: 10.1159/000276710. Epub 2010 May 5. Review.

Rapamycin treatment augments motor neuron degeneration in SOD1(G93A) mouse model of amyotrophic lateral sclerosis.

Zhang X, Li L, Chen S, Yang D, Wang Y, Zhang X, Wang Z, Le W.

Autophagy. 2011 Apr;7(4):412-25. Epub 2011 Apr 1.

Prenatal hypoxia may aggravate the cognitive impairment and Alzheimer's disease neuropathology in APPSwe/PS1A246E transgenic mice.

Zhang X, Li L, Zhang X, Xie W, Li L, Yang D, Heng X, Du Y, Doody RS, Le W.

Neurobiol Aging. 2013 Mar;34(3):663-78. doi: 10.1016/j.neurobiolaging.2012.06.012. Epub 2012 Jul 15.

MicroRNA-23a/b and microRNA-27a/b suppress Apaf-1 protein and alleviate hypoxia-induced neuronal apoptosis.

Chen Q, Xu J, Li L, Li H, Mao S, Zhang F, Zen K, Zhang CY, Zhang Q.

Cell Death Dis. 2014 Mar 20;5:e1132. doi: 10.1038/cddis.2014.92.

Tumor-secreted miR-214 induces regulatory T cells: a major link between immune evasion and tumor growth.

Yin Y, Cai X, Chen X, Liang H, Zhang Y, Li J, Wang Z, Chen X, Zhang W, Yokoyama S, Wang C, Li L, Li L, Hou D, Dong L, Xu T, Hiroi T, Yang F, Ji H, Zhang J, Zen K, Zhang CY.

Cell Res. 2014 Oct;24(10):1164-80. doi: 10.1038/cr.2014.121. Epub 2014 Sep 16.

Immune modulatory function of abundant immune-related microRNAs in microvesicles from bovine colostrum.

Sun Q, Chen X, Yu J, Zen K, Zhang CY, Li L.

Protein Cell. 2013 Mar;4(3):197-210. doi: 10.1007/s13238-013-2119-9. Epub 2013 Mar 13.

MicroRNA-29a modulates axon branching by targeting doublecortin in primary neurons.

Li H, Mao S, Wang H, Zen K, Zhang C, Li L.

Protein Cell. 2014 Feb;5(2):160-9. doi: 10.1007/s13238-014-0022-7. Epub 2014 Feb 18.

miR-17 regulates the proliferation and differentiation of the neural precursor cells during mouse corticogenesis.

Mao S, Li H, Sun Q, Zen K, Zhang CY, Li L.

FEBS J. 2014 Feb;281(4):1144-58. doi: 10.1111/febs.12680. Epub 2014 Jan 15.

Role of miR-17 family in the negative feedback loop of bone morphogenetic protein signaling in neuron.

Sun Q, Mao S, Li H, Zen K, Zhang CY, Li L.

PLoS One. 2013 Dec 11;8(12):e83067. doi: 10.1371/journal.pone.0083067. eCollection 2013.

Secreted miR-34a in astrocytic shedding vesicles enhanced the vulnerability of dopaminergic neurons to neurotoxins by targeting Bcl-2.

Mao S, Sun Q, Xiao H, Zhang C, Li L.

Protein Cell. 2015 Jul;6(7):529-540. doi: 10.1007/s13238-015-0168-y. Epub 2015 Jun 20.

miR-17-92 facilitates neuronal differentiation of transplanted neural stem/precursor cells under neuroinflammatory conditions.

Mao S, Li X, Wang J, Ding X, Zhang C, Li L.

J Neuroinflammation. 2016 Aug 27;13(1):208. doi: 10.1186/s12974-016-0685-5.

Zika virus infected primary microglia impairs NPCs proliferation and differentiation.

Wang J, Liu J, Zhou R, Ding X, Zhang Q, Zhang C, Li L.

Biochem Biophys Res Commun. 2018 Mar 4;497(2):619-625. doi: 10.1016/j.bbrc.2018.02.118. Epub 2018 Feb 15.

Dendritic targeted mRNA expression via a cis-acting RNA UTR element.

Lu L, Zhang F, Li Y, Yang A, Guan C, Ding X, Liu Y, Liu Y, Zhang CY, Li L, Zhang Q.

Biochem Biophys Res Commun. 2019 Feb 5;509(2):402-406. doi: 10.1016/j.bbrc.2018.12.137. Epub 2018 Dec 26.

A Simple System for Differentiation of Functional Intestinal Stem Cell-like Cells from Bone Marrow Mesenchymal Stem Cells.

Ye L, Sun LX, Wu MH, Wang J, Ding X, Shi H, Lu SL, Wu L, Wei J, Li L, Wang YF.

Mol Ther Nucleic Acids. 2018 Dec 7;13:110-120.

Wang, Jin; Ding, Xin; Wu, Xiangyu; Liu, Jing; Zhou, Rui; Wei, Pingxuan;Zhang, Qipeng; Zhang, Chenyu; Zen, Ke*; Li, Liang*; SIRP alpha deficiency accelerates the pathologic process in models of Parkinson disease , GLIA, 2019, 67(12): 2343-2359. 

Zhen Zhou, Yu Zhou, Xia-Ming Jiang, Yanbo Wang, Xi Chen, Gengfu Xiao, Chen-Yu Zhang, Yongxiang Yi,Lei-Ke Zhang and Liang Li; Decreased HD-MIR2911 absorption in human subjects with the SIDT1 polymorphism fails to inhibit SARS-CoV-2 replication. Cell Discovery. 2020 https://doi.org/10.1038/s41421-020-00206-5 www.

Ding, Xin; Wang, Jin; Huang, Miaoxin; Chen, Zhangpeng; Liu, Jing; Zhang, Qipeng; Zhang, Chenyu; Xiang, Yang; Zen, Ke*; Li, Liang*; Loss of microglial SIRPα promotes synaptic pruning in preclinical models of neurodegeneration. , Nature Communications, 2021, 12(1): 0-2030.

2008年度上海医学科技奖二等奖

2008年度中华医学奖二等奖