公开(公告)号：US08580512B2

公开(公告)日：2013-11-12

申请号：US13063865

申请日：2009-11-20

申请人： Stevan Marcus ,  Galina Gulis ,  P. Connor Johnson

发明人： Stevan Marcus ,  Galina Gulis ,  P. Connor Johnson

IPC分类号： C12Q1/68

CPC分类号： C12Q1/04 ,  G01N2333/395 ,  G01N2800/2835

摘要： The disclosure encompasses methods for the screening of small molecules or nucleic acids that may reverse the inhibition of growth of the unicellular yeast Schizosaccharomyces pombe by rotenone. The use of a yeast as the screening target allows for the high-throughput screening of small molecule and nucleic acid libraries for candidates that may then be screened in animal models as therapeutic agents for the treatment of neurodegenerative diseases. The plant-derived isoflavonoid, rotenone, while only moderately inhibitory to S. pombe cell growth on complex rich medium, is highly inhibitory to growth on synthetic minimal medium. S. pombe cells carrying a deletion in the gene pmk1 are hypersensitive to rotenone. S. pombe, therefore, provides a model for elucidating complex 1-independent targets of rotenone, and can serve as a screening tool for identifying compounds or oligonucleotides potentially able to reverse the effects of rotenone or Parkinson's disease in animal or human subjects.

摘要翻译： 本公开包括用于筛选小分子或核酸的方法，所述小分子或核酸可以通过鱼藤酮来抑制单细胞酵母粟酒裂殖酵母的生长的抑制。 使用酵母作为筛选靶标允许对可能在动物模型中筛选的候选物的小分子和核酸文库的高通量筛选作为治疗神经变性疾病的治疗剂。 植物来源的异黄酮，鱼藤酮，而对富含复合物的培养基上的S.pombe细胞生长只有适度抑制，对合成基本培养基的生长具有高度的抑制作用。 在基因pmk1中携带缺失的粟酒酵母细胞对鱼藤酮具有过敏性。 因此，S.pombe提供了用于阐明鱼藤酮的复合物1-非依赖性靶标的模型，并且可以用作鉴定在动物或人类受试者中潜在地能够逆转鱼藤酮或帕金森病的作用的化合物或寡核苷酸的筛选工具。

公开(公告)号：US20110250607A1

公开(公告)日：2011-10-13

申请号：US13063865

申请日：2009-11-20

申请人： Stevan Marcus ,  Galina Gulis ,  P.Connor Johnson

发明人： Stevan Marcus ,  Galina Gulis ,  P.Connor Johnson

IPC分类号： C12Q1/68 ,  C12Q1/02

CPC分类号： C12Q1/04 ,  G01N2333/395 ,  G01N2800/2835

摘要： The disclosure encompasses methods for the screening of small molecules or nucleic acids that may reverse the inhibition of growth of the unicellular yeast Schizosaccharomyces pombe by rotenone. The use of a yeast as the screening target allows for the high-throughput screening of small molecule and nucleic acid libraries for candidates that may then be screened in animal models as therapeutic agents for the treatment of neurodegenerative diseases. The plant-derived isoflavonoid, rotenone, while only moderately inhibitory to S. pombe cell growth on complex rich medium, is highly inhibitory to growth on synthetic minimal medium. S. pombe cells carrying a deletion in the gene pmk1 are hypersensitive to rotenone. S. pombe, therefore, provides a model for elucidating complex 1-independent targets of rotenone, and can serve as a screening tool for identifying compounds or oligonucleotides potentially able to reverse the effects of rotenone or Parkinson's disease in animal or human subjects.

摘要翻译： 本公开包括用于筛选小分子或核酸的方法，所述小分子或核酸可以通过鱼藤酮来抑制单细胞酵母粟酒裂殖酵母的生长的抑制。 使用酵母作为筛选靶标允许对可能在动物模型中筛选的候选物的小分子和核酸文库的高通量筛选作为治疗神经变性疾病的治疗剂。 植物来源的异黄酮，鱼藤酮，而对富含复合物的培养基上的S.pombe细胞生长只有适度抑制，对合成基本培养基的生长具有高度的抑制作用。 在基因pmk1中携带缺失的粟酒酵母细胞对鱼藤酮具有过敏性。 因此，S.pombe提供了用于阐明鱼藤酮的复合物1-非依赖性靶标的模型，并且可以用作鉴定在动物或人类受试者中潜在地能够逆转鱼藤酮或帕金森病的作用的化合物或寡核苷酸的筛选工具。