李靚

2012-至今，中國神經科學學會會員

FEBS J，Journal of Neuroinflammation，Neurobiology of Aging等雜誌審稿專家 ^[1] 

1.老年性神經退行性疾病發病機制研究

老年性神經退行性疾病主要包括帕金森病(PD)和阿爾茨海默病(AD)。PD是多巴胺(DA)神經元的丟失導致運動能力衰退，本課題組主要研究膠質細胞在PD發病過程中對DA神經元的作用機制。AD是一種中樞神經系統變性病,起病隱襲,病程呈慢性進行性,是老年期痴呆最常見的一種類型。AD病理目前的假説是澱粉樣肽和tau蛋白沉積，但是目前針對澱粉樣肽的藥物開發並不理想，近年來最新的研究顯示，小膠質細胞介導的突觸清除異常是AD臨牀認知記憶功能衰退的關鍵，本課題組主要研究小膠質細胞突觸清除的調控機制及干預，尋找治療AD的潛在藥物。

2.神經膠質瘤發病機制及干預研究

神經膠質瘤是是最常見的原發性中樞神經系統腫瘤，在膠質瘤周圍存在大量的小膠質細胞(microglia)和巨噬細胞(macrophage)稱為GAMM，上述細胞在生理狀態下具有很強的吞噬能力，但是在腫瘤周圍其能力變弱，本課題組主要研究如何調節干預GAMM的功能，利用腫瘤免疫的原理提高GAMM對腫瘤細胞的吞噬，減緩腫瘤的發生發展。 ^[1] 

2008年度上海醫學科技獎二等獎

2008年度中華醫學獎二等獎 ^[1] 

代表性研究論文：

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. ^[1]