柯尊記

長期從事衰老的神經生物學機制研究，發現了氧化代謝紊亂、氧自由基產生增加、免疫/炎症反應是維生素B1缺乏（TD）引起的選擇性中線旁丘腦核神經元死亡的重要病理生理過程；內質網應激、未摺疊和錯誤摺疊蛋白累積、caspase-12激活是參與代謝性氧化損傷引起的神經元死亡的主要細胞機制；證實神經元產生的單核細胞趨化因子，是氧化代謝紊亂誘發免疫/炎症反應的開關分子。發現氧化代謝紊亂可以通過增強β分泌酶的活性增加β澱粉樣蛋白的產生，從而加速神經元病變的發展過程。TD可增加澱粉樣蛋白的產生，亞臨床維生素B1缺乏是老年性痴呆的危險因素之一。

基本介紹

• 中文名：柯尊記
• 性別：男
• 民族：漢
• 職業：教師
• 國家：中國

個人簡介：

1996年於中山大學醫學院解剖學與神經生物學專業獲博士。先後在中國科學院上海腦研究所，美國伊利偌斯大學醫學院解剖學與細胞生物學系和美國康奈爾大學醫學院神經科學系從事博士後研究。1998-1999年任鄖陽醫學院副教授，解剖學教研室主任。2003年底加入中國科學院上海生科院營養科學研究所，2004年入選中國科學院“百人計畫”。2006年入選上海市“浦江人才計畫”。現任中國科學院上海生命科學研究院營養科學研究所研究員，博士研究生導師，神經營養科學研究組組長。

研究領域：

1)中西醫結合防治神經退行性疾病。在傳統中藥中尋找可以延緩老年性神經退行性疾病發展的生物活性小分子和中藥複方。為防治老年性神經退行性疾病，尤其是阿爾茨海默病提供策略和方法。

2)闡明老年性神經元死亡的可能細胞、分子生物學機制，尋找能客觀反映老齡健康的生物學標記，和延緩老年性神經元死亡的分子靶點。

3)探討酒精濫用等環境因素對神經系統發育和衰老影響的細胞、分子生物學機制。

近期論文：

Xu DQ, Wang Z, Wang CY, Zhang DY, Wan HD, Zhao ZL, Gu J, Zhang YX, Li ZG, Man KY, Pan Y, Wang ZF, Ke ZJ, Liu ZX, Liao LJ, Chen Y. PAQR3 controls autophagy by integrating AMPK signaling to enhance ATG14L-associated PI3K activity.The EMBO Journal(2016) 35: 496–514.

Klionsky DJ,… , Ke ZJ,…, Zughaier SM. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).Autophagy. 2016 Jan 2;12(1):1-222.

Xu M, Wang S, Ren Z, Frank JA, Yang XH, Zhang Z, Ke ZJ, Shi X, Luo J.Chronic ethanol exposure enhances the aggressiveness of breast cancer: the role of p38γ.Oncotarget. 2015 Dec 7. doi: 10.18632/oncotarget.6508. [Epub ahead of print]

Wang H, Wang X, Ke ZJ, Comer AL, Xu M, Frank JA, Zhang Z, Shi X, Luo J. Tunicamycin-induced unfolded protein response in the developing mouse brain. ToxicolApplPharmacol. 2015 Mar 15;283(3):157-67.

Yong Y, Meng Y, Ding H, Fan Z, Tang Y, Zhou C, Luo J, Ke ZJ*. PACT/RAX Regulates the Migration of Cerebellar Granule Neurons in the Developing Cerebellum. Sci Rep. 2015 Jan 22;5:7961.

Ke ZJ*, Luo J. Response to Comment on "Thiamine Deficiency Promotes T Cell Infiltration in Experimental Autoimmune Encephalomyelitis: The Involvement of CCL2". J Immunol.2014 Nov 15;193(10):4755-6.

Ji Z, Fan Z, Zhang Y, Yu R, Yang H, Zhou C, Luo J, Ke ZJ*. Thiamine Deficiency Promotes T Cell Infiltration in Experimental Autoimmune Encephalomyelitis: The Involvement of CCL2. J Immunol. 2014 Sep 1;193(5):2157-67.

Liu M, Alimov AP, Wang H, Frank JA, Katz W, Xu M, Ke ZJ, Luo J. Thiamine deficiency induces anorexia by inhibiting hypothalamic AMPK. Neuroscience.2014 Mar 5;267:102-113

Wang F, Chen H, Sun XJ,Ke ZJ*. Improvement of cognitive deficits in SAMP8 mice by 3-n-butylphthalide. Neurol Res. 2014 Mar;36(3):224-33.

Wang H, Ke ZJ, Alimov A, Xu M, Frank JA, Fang S, Luo J. Spatiotemporal Expression of MANF in the Developing Rat Brain. PLoS One. 2014 Feb 28;9(2):e90433.

Meng Y, Yong Y, Yang G, Ding H, Fan Z, Tang Y, Luo J, Ke ZJ*.Autophagy alleviates neurodegeneration caused by mild impairment of oxidative metabolism. J Neurochem. 2013 Sep;126(6):805-18.

Li W, Tang Y, Fan Z, Meng Y, Yang G, Luo J, Ke ZJ*. Autophagy is involved in oligodendroglial precursor-mediated clearance of amyloid peptide. MolNeurodegener. 2013 Aug 10;8:27.

Zhang G, Ding H, Chen H, Ye X, Li H, Lin X, Ke ZJ*. Thiamine Nutritional Status and Depressive Symptoms Are Inversely Associated among Older Chinese Adults. J Nutr.2013 Jan;143(1):53-8.

Chen G, Ke ZJ, Xu M, Liao M, Wang X, Qi Y, Zhang T, Frank JA, Bower KA, Shi X, Luo J. Autophagy is a protective response to ethanol neurotoxicity. Autophagy. 2012 Nov;8(11):1577-89

Wang X, Ke ZJ, Chen G, Xu M, Bower KA, Frank JA, Zhang Z, Shi X, Luo J. Cdc42-dependent activation of NADPH oxidase is involved in ethanol-induced neuronal oxidative stress. PLoS One. 2012;7(5):e38075.

Wang X, Mandal AK, Saito H, Pulliam JF, Lee EY, Ke ZJ, Lu J, Ding S, Li L, Shelton BJ, Tucker T, Evers BM, Zhang Z, Shi X. Arsenic and chromium in drinking water promote tumorigenesis in a mouse colitis-associated colorectal cancer model and the potential mechanism is ROS-mediated Wnt/β-catenin signaling pathway. ToxicolApplPharmacol.2012 Jul 1;262(1):11-21

Wang S, Xu M, Li F, Wang X, Bower KA, Frank JA, Lu Y, Chen G, Zhang Z, Ke Z, Shi X, Luo J. Ethanol promotes mammary tumor growth and angiogenesis: the involvement of chemoattractant factor MCP-1. Breast Cancer Res Treat. 2012 Jun;133(3):1037-48

Ji Z,Ke ZJ, Geng JG. SAP suppresses the development of experimental autoimmune encephalomyelitis in C57BL/6 mice.Immunol Cell Biol. 2012 Apr;90(4):388-95.

Sun X, Xiong Z, Zhang Y, Meng Y, Xu G, Xia Z, Li J, Zhang R, Ke Z, Xia Z, Hu Y. Harpagoside attenuates MPTP/MPP(+) induced dopaminergic neurodegeneration and movement disorder via elevating glial cell line-derived neurotrophic factor. J Neurochem.2012 Mar;120(6):1072-83

Wang X, Son YO, Chang Q, Sun L, Hitron JA, Budhraja A, Zhang Z, Ke Z, Chen F, Luo J, Shi X. NADPH oxidase activation is required in reactive oxygen species generation and cell transformation induced by hexavalent chromium. Toxicol Sci.2011 Oct;123(2):399-410.

Ke ZJ, Wang X, Liu Y, Fan Z, Chen G, Xu M, Bower KA, Fank JA, Li M, Fang S, Shi X, Luo J. Ethanol Induces Endoplasmic Reticulum Stress in the Developing Brain. Alcohol ClinExp Res. 2011;35(9): 1574–1583.

Ke ZJ, Liu Y, Wang X, Fan Z, Chen G, Xu M, Bower KA, Frank JA, Ou X, Shi X, Luo J. Cyanidin-3-glucoside ameliorates ethanol neurotoxicity in the developing brain. J Neurosci Res.2011 Oct;89(10):1676-84.

Zhang Z, Li W, Cheng S, Yao H, Zhang F, Chang Q, Ke ZJ, Wang X, Son YO, Luo J, Shi X. Nickel-induced Down-regulation of ΔNp63 and its Role in The Proliferation of Keratinocytes. ToxicolApplPharmacol.2011 Jun 15;253(3):235-43.

Yang G, Meng Y, Li W, Yong Y, Fan Z, Ding HQ, Wei YZ, Luo J, Ke ZJ*. Neuronal MCP-1 Mediates Microglia Recruitment and Neurodegeneration Induced by the Mild Impairment of Oxidative Metabolism. Brain Pathol. 2011;21(3):279-297.

Yong Y, Ding H, Fan Z, Luo J, Ke ZJ*. Lithium Fails to Protect Dopaminergic Neurons in the 6-OHDA Model of Parkinson's disease. Neurochem Res. 2011, 36(3):367-74.

Lee SC, Yang G, Liu Y, Zhao L, Xu J, Zhang X, Wan Y, Feng C, Fan ZQ, Liu Y, Luo J, Ke ZJ*. ADAR2-dependent RNA editing of GluR2 is involved in thiamine deficiency-induced alteration of calcium dynamics. Mol Neurodeger. 2010, 5:54. (27 November 2010)

Xu M, Bower KA, Wang S, Frank JA, Chen G, Ding M, Wang S, Shi X, Ke ZJ, Luo J. Cyanidin-3-Glucoside Inhibits Ethanol-induced Invasion of Breast Cancer Cells Overexpressing ErbB2. Mol. Cancer2010 Oct 29;9:285.

Zhang QP, Yang G, Li WX, Fan Z, Sun AY, Luo J, Ke ZJ*. Thiamine deficiency increases b-secretase activity and accumulation of β-amyloid peptides. Neurobiol. Aging. 2011;32(1):42-53.

Wang X, Meng D, Chang Q, Pan J, Zhang Z, Chen G, Ke ZJ, Luo J, Shi X. Arsenic Inhibits Neurite Outgrowth by Inhibiting LKB1-AMPK Signaling Pathway. Environ Health Perspect. 2010;118(5):627-34.

Xu M, Bower KA, Chen G, Shi X, Dong Z, Ke ZJ, Luo J. Ethanol Enhances the Interaction of Breast Cancer Cells Over-Expressing ErbB2 with Fibronectin. Alcohol Clin Exp Res. 2010;34(5):751-60.

Xu G, Xiong Z, Yong Y, Wang Z, Ke ZJ, Xia Z, Hu Y. Catalpol attenuates MPTP induced neuronal degeneration of nigral-striatal dopaminergic pathway in mice through elevating glial cell derived neurotrophic factor in striatum. Neuroscience. 2010;167(1):174-84.

You J, Yu Y, Jiang L, Li W, Yu X, Gonzalez L, Yang G, Ke ZJ, Li W, Li C, Liu Y. Signaling through Tyr985 of Leptin Receptor as an Age/diet-dependent Switch in the Regulation of Energy Balance. Mol Cell Biol. 2010;30(7):1650-9.

Ke ZJ, Wang X, Fan Z, Luo J. Ethanol promotes thiamine deficiency-induced neuronal death: involvement of double-stranded RNA-activated protein kinase. Alcohol Clin Exp Res. 2009;3 3(6):1097-103.

Chen, G., Bower, KA., Xu, M., Ding, M., Wang SY., Shi, X., Ke, ZJ., Luo, J. Cyaniding-3-glucoside reverses ethanol-induced inhibition of neurite outgrowth: role of glycogen synthase 3 beta. Neurotox. Res. 2009, 15:321-331.

Liu Y., Chen, G., Ma, C., Bower, KA., Xu, M., Fan, Z., Shi, X., Ke, ZJand Luo, J. Over-expression of GSK3beta sensitizes neuronal cells to ethanol toxicity. J. Neurosci Res. 2009; 87: 2793-2802.

Zhang, Q., Ding, H., Li, W., Fan, Z., Sun, A., Luo, J., Ke, ZJ*. Senscence accelerated mouse strain is sensitive to neurodegeneration induced by mild impairment of oxidative metabolism. Brain Res. 2009; 1264: 111-118.

Chen YY, Chen G, Fan Z, Luo J, Ke ZJ. GSK3beta and endoplasmic reticulum stress mediate rotenone-induced death of SK-N-MC neuroblastoma cells. Biochem Pharmacol. 2008; 76(1):128-138.

Ma C, Bower KA, Chen G, Shi X, Ke ZJ, Luo J. Interaction between ERK and GSK3beta mediates basic fibroblast growth factor-induced apoptosis in SK-N-MC neuroblastoma cells. J Biol Chem. 2008; 283(14):9248-56.

Chen G, Ma C, Bower KA, Shi X, Ke ZJ, Luo J. Ethanol promotes endoplasmic reticulum stress-induced neuronal death: Involvement of oxidative stress. J Neurosci Res. 2008; 86(4):937-46.

Wang X, Fan ZQ, Wang B, Luo J, Ke ZJ. Activation of PKR by mild impairment of oxidative metabolism in neurons. J Neurochem. 2007, 103(6):2380-2390.

Ma C, Wang J, Gao Y, Gao TW, Chen G, Bower KA, Odetallah M, Ding M, Ke ZJ, Luo J. The Role of Glycogen Synthase Kinase 3 beta in the Transformation of Epidermal Cells. Cancer Res. 2007, 67(16):7756-64.

Cai G, Wang J, Xin X, Ke ZJ, Luo J. Phosphorylation of Glycogen Synthase Kinase-3 beta at Serine 9 Confers Cisplatin Resistance in Ovarian Cancer Cells. Int J Oncol. 2007, 31(3):657-62.

Chen G, Fan ZQ, Wang X, Ma C, Bower KA, Shi X, Ke ZJ, Luo J. Brain-derived Neurotrophic Factor Suppresses Tunicamycin-induced Upregulation of CHOP in Neurons. J Neurosci Res. 2007, 85(8):1674-1684.

Wang X, Wang BW, Fan ZQ, Shi XL, Ke ZJ, and Luo J. Thiamine Deficiency Induces Endoplasmic Reticulum Stress in Neurons. Neurosciences. 2007, 144(3):1045-56.