公开(公告)号：US20140186357A1

公开(公告)日：2014-07-03

申请号：US14021210

申请日：2013-09-09

申请人： KOREA CENTER FOR DISEASE CONTROL AND PREVENTION

发明人： Young Ho Koh ,  Sang Moon Yun ,  Sun-Jung Cho ,  Chulman Jo ,  Sangmee Ahn ,  Jae Chun Song ,  Sung Yeon Song

IPC分类号： C12N15/113 ,  G01N33/50 ,  G01N33/68 ,  C12Q1/68 ,  A61K38/02 ,  A61K39/395

CPC分类号： C12N15/1138 ,  A61K38/43 ,  C12N15/1137 ,  C12N2310/11 ,  C12N2310/14 ,  C12N2310/16 ,  C12N2310/531 ,  C12Q1/6883 ,  C12Q2600/112 ,  C12Q2600/158 ,  C12Y304/23046 ,  G01N33/6896 ,  G01N2500/10

摘要： A treatment method for degenerative brain disorders using a pharmaceutically effective dose of the inhibitor of SUMO1 (small ubiquitin-like modifier 1) and BACE1 (β-secretase) interaction, or the inhibitor of SUMO1 expression or activation is provided. More specifically, it was confirmed that SUMO1 increased BACE1 accumulation and Aβ generation, that is SUMO1 regulated BACE1 accumulation by interacting with BACE1, and BACE1 dileucine motif was involved in SUMO1-mediated BACE1 accumulation. In addition, SUMO1 protein induced autophagy in H4 cells, while SUMO1 depletion reduced LC3-II level. It was further confirmed that SUMO1 and LC3 were co-localized in the cortex of APP transgenic mice. As shown herein, a pharmaceutically effective dose of the inhibitor of SUMO1 and BACE1 interaction or the inhibitor of SUMO1 expression can be effectively used for the treatment of degenerative brain disorders.

摘要翻译： 提供了使用药学有效剂量的SUMO1抑制剂（小泛素样修饰物1）和BACE1（＆amp;分泌酶）相互作用或SUMO1表达或激活抑制剂的退行性脑病的治疗方法。 更具体地说，证实了SUMO1增加了BACE1的积累和A＆bgr; 一代，即SUMO1通过与BACE1相互作用调节BACE1的积累，BACE1二亚氨酸基序参与SUMO1介导的BACE1积累。 此外，SUMO1蛋白在H4细胞中诱导自噬，而SUMO1消耗降低LC3-II水平。 进一步证实，SUMO1和LC3共定位于APP转基因小鼠的皮质中。 如本文所示，药物有效剂量的SUMO1和BACE1相互作用的抑制剂或SUMO1表达的抑制剂可以有效地用于治疗退行性脑病。