PGC-1 as Therapeutic target for Neurodegenerative Diseases

报告摘要：
线粒体功能障碍是大脑老化及神经退行性疾病的一个共同特征。线粒体调节蛋白过氧化物酶体增殖物激活受体gamma共激活因子1 (PGC-1alpha) 通过与核受体和特异转录因子的结合在细胞线粒体生成，能量代谢， 和抗氧化应急相关基因的表达调控中起到重要作用。报告将着重介绍PGC-1alpha分子在大脑和神经细胞中的的生物学功能，PGC-1alpha 转录调控异常与线粒体功能缺损在亨廷顿氏病(HD)神经损伤中的关系， 以及PGC-1alpha作为治疗神经退行性疾病的靶标其神经保护作用。

报告人简介：
崔立斌，博士，1987年毕业于南开大学生物系遗传学专业；1995年毕业于中国军事医学科学院生物工程研究所, 获得有分子遗传医学博士学位；2000-2003 美国马里兰州立大学(University of Maryland)营养科学系研究助理；2003-2009美国哈佛大学医学院麻省总医院神经退行性疾病研究所博士后研究员，讲师；2009-2010美国内布拉斯加州立大学医学中心药理和实验神经学系助教授；2010年至今美国美国波士顿大学医学院药理和试验药物学系助教授。主要从事神经退行性疾病遗传模型建立和分子致病机理研究。其在该领域有关PGC-1alpha在神经系统线粒体生成和能量代谢中生物学功能的研究为亨廷顿氏病(HD)和其它神经退行性疾病的药物研发和治疗开启了新的思路。许多研究成果发表在 Cell, Cell Metabolism, J. Neuroscience, J Neuroscience Methods,和 PNAS等核心期刊。

代表性文章：
1. Cohen DE, Jeong H, Cui L, Supinski A, Bordone L, Guarente LP, and Krainc D. Sirt1 mediates neuroprotection from mutant huntingtin by activation of TORC1 and CREB transcriptional pathway, Nature Medicine (accepted; 2011)
2.Xiang Z, Valenza M, Cui L, Leoni V, Jeong HK, Brilli E, Zhang J, Peng Q, Duan W, Reeves SA, Cattaneo E, Krainc D.Peroxisome-proliferator-activated receptor gamma coactivator 1 α contributes to dysmyelination in experimental models of Huntington's disease. J Neurosci. 2011 Jun 29;31(26):9544-53
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4.Jeong H, Then F, Melia TJ Jr, Mazzulli JR, Cui L, Savas JN, Voisine C, Paganetti P, Tanese N, Hart AC, Yamamoto A, Krainc D. Acetylation targets mutant huntingtin to autophagosome for degradation. Cell, 2009, 137(1):60-72
5. Cui L, Jeong H, Borovecki F, Parkhurst CN, Tanese N, and Krainc D. Transcriptional Repression of PGC-1alpha by Mutant Huntingtin Leads to Mitochondrial Dysfunction and Neurodegeneration. Cell, 2006, 127:59-69
6.Weydt P, Pineda VV, Torrence AE, Libby RT, Satterfield TF, Lazarowski ER, Gilbert ML, Morton GJ, Bammler TK, Strand AD, Cui L, Beyer RP, Easley CN, Smith AC, Krainc D, Luquet S, Sweet IR, Schwartz MW, La Spada AR. Thermoregulatory and metabolic defects in Huntington's disease transgenic mice implicate PGC-1alpha in Huntington's disease neurodegeneration. Cell Metabolism, 2006, 4:349-62
7. Lin T, Xiang Z, Cui L, Stallcup W, Reeves SA. New mouse oligodendrocyte precusor (mOP) cells for studies on oligodendrocyte maturation and function. J Neurosci Methods, 2006; 157(2): 187-94
8.Zhai W, Jeong H, Cui L, Krainc D, Tjian R. In vitro analysis of huntingtin-mediated transcriptional repression reveals multiple transcription factor targets. Cell, 2005, 123:1241-53
9. Lin J, Wu PH, Tarr PT, Lindenberg KS, St-Pierre J, Zhang CY, Mootha VK, Jager S, Vianna CR, Reznick RM, Cui L, Manieri M, Donovan MX, Wu Z, Cooper MP, Fan MC, Rohas LM, Zavacki AM, Cinti S, Shulman GI, Lowell BB, Krainc D, Spiegelman BM. Defects in adaptive energy metabolism with CNS-linked hyperactivity in PGC-1alpha null mice. Cell, 2004, 119:121-35