公开(公告)号：US20110064721A1

公开(公告)日：2011-03-17

申请号：US12667832

申请日：2008-07-02

申请人： Jianhua Zhang ,  Guy Caldwell ,  Kevin Roth ,  David Standaert ,  Kim Cladwell ,  Shusei Hamamichi

发明人： Jianhua Zhang ,  Guy Caldwell ,  Kevin Roth ,  David Standaert ,  Kim Cladwell ,  Shusei Hamamichi

IPC分类号： A61K39/395 ,  C12Q1/37 ,  A61K38/02 ,  A61P25/28 ,  A61P25/16 ,  A61K31/7088 ,  C12Q1/68 ,  A61K38/48

CPC分类号： A61K31/47 ,  A61K38/488 ,  G01N33/5023 ,  G01N33/5088

摘要： Provided herein are methods and compositions for promoting neuroprotection in a subject and for treating a neural disorder associated with protein aggregation comprising administering to the subject an agent that increases expression or activity of cathepsin-D. Also provided are methods of screening for agents that increase expression or activity of cathepsin-D and methods of screening for neuroprotective agents.

摘要翻译： 本文提供用于促进受试者中神经保护作用并用于治疗与蛋白质聚集相关的神经障碍的方法和组合物，包括向受试者施用增加组织蛋白酶D的表达或活性的试剂。 还提供了筛选增加组织蛋白酶-D的表达或活性的试剂的方法和筛选神经保护剂的方法。

公开(公告)号：US20050227279A1

公开(公告)日：2005-10-13

申请号：US11140127

申请日：2005-05-27

申请人： Guy Caldwell ,  Kim Caldwell

发明人： Guy Caldwell ,  Kim Caldwell

IPC分类号： A61K38/00 ,  C07K14/47 ,  C07K16/18 ,  C12Q1/68 ,  C07H21/04

CPC分类号： C07K16/18 ,  A61K38/00 ,  C07K14/47 ,  C12Q1/6883 ,  C12Q2600/156 ,  C12Q2600/158 ,  G01N2500/04

摘要： The invention relates to polynucleotides comprising polynucleotide sequences corresponding to the tor-1, tor-2, ooc-5, DYT1, and DYT2 genes and parts thereof that encode polypeptide sequences and parts thereof possessing varying degrees of torsin activity, and methods of screening and amplifying polynucleotides encoding polypeptide sequences which encode polypeptides having varying degrees of TOR-1, TOR2, OOC-5 TOR-A, and TOR-B activity. Further, the invention relates to methods of reducing protein aggregation, methods of treating diseases that are caused by protein aggregation, methods of screening potential protein-aggregation-reducing products, methods of screening potential therapeutics of diseases caused by protein aggregation, and pharmaceuticals, therapeutics, and kits comprising polynucleotide sequences corresponding to the tor-1, tor-2, ooc-5, DYT1, and DYT2 genes and/or polypeptides having torsin activity.

摘要翻译： 本发明涉及多核苷酸，其包含对应于tor-1，tor-2，ooc-5，DYT1和DYT2基因的多核苷酸序列及其部分，其编码具有不同程度的躯干活性的多肽序列及其部分，以及筛选和 扩增编码多肽序列的多核苷酸，其编码具有不同程度的TOR-1，TOR2，OOC-5TOR-A和TOR-B活性的多肽。 此外，本发明涉及减少蛋白质聚集的方法，治疗由蛋白质聚集引起的疾病的方法，筛选潜在的蛋白质聚集减少产品的方法，筛选由蛋白质聚集引起的疾病的潜在治疗剂的方法以及药物，治疗剂 ，以及包含对应于具有抗转录活性的tor-1，tor-2，ooc-5，DYT1和DYT2基因和/或多肽的多核苷酸序列的试剂盒。

公开(公告)号：US20070203079A1

公开(公告)日：2007-08-30

申请号：US11603924

申请日：2006-11-21

申请人： Guy Caldwell ,  Kim Caldwell ,  Songsong Cao

发明人： Guy Caldwell ,  Kim Caldwell ,  Songsong Cao

IPC分类号： A61K31/7048 ,  A61K31/704 ,  A61K31/4741 ,  A61K31/4745 ,  A61K31/404

CPC分类号： A61K31/7048 ,  A61K31/00 ,  A61K31/404 ,  A61K31/4741 ,  A61K31/4745 ,  A61K31/704

摘要： Methods are provided for preventing neurodegeneration and neuronal loss by administering compositions comprising small molecule compounds with the effect of preventing neurodegeneration and neuronal loss. In one aspect of the invention, the methods and compositions are also useful for treating neurodegenerative diseases. Small molecule compounds provide an important treatment option because of their stability, ease of use in both manufacture and formulation, ease of administration, and patient compliance. The small molecule compound compositions of the present invention may include topoisomerase II inhibitors, bacterial transpeptidase inhibitors, calcium channel antagonists, cyclooxygenase inhibitors, folic acid synthesis inhibitors, or sodium channel blockers and functional analogues thereof that have an effect on neurodegeneration. The compositions of the present invention may be administered prophylactically before the onset of clinical symptoms or after clinical symptoms of a neurodegenerative disease have manifested.

摘要翻译： 提供了通过施用包含小分子化合物的组合物来预防神经变性和神经元损失的方法，其具有预防神经变性和神经元损失的作用。 在本发明的一个方面，所述方法和组合物也可用于治疗神经变性疾病。 小分子化合物提供了重要的治疗选择，因为它们的稳定性，制造和制剂易于使用，易于施用和患者依从性。 本发明的小分子化合物组合物可以包括对神经变性有影响的拓扑异构酶II抑制剂，细菌转肽酶抑制剂，钙通道拮抗剂，环加氧酶抑制剂，叶酸合成抑制剂或其钠通道阻滞剂及其功能类似物。 本发明的组合物可以在临床症状发作之前或在神经退行性疾病的临床症状已经显现之后进行预防性施用。

公开(公告)号：US20060068472A1

公开(公告)日：2006-03-30

申请号：US11282495

申请日：2005-11-18

申请人： Guy Caldwell ,  Kim Caldwell

发明人： Guy Caldwell ,  Kim Caldwell

IPC分类号： C07K14/705 ,  C12Q1/68 ,  A01K67/033 ,  C07H21/04

CPC分类号： C07K16/18 ,  A61K38/00 ,  C07K14/47 ,  C12Q1/6883 ,  C12Q2600/156 ,  C12Q2600/158 ,  G01N2500/04

摘要： The invention relates to polynucleotides comprising polynucleotide sequences corresponding to the tor-1, tor-2, ooc-5, DYT1, and DYT2 genes and parts thereof that encode polypeptide sequences and parts thereof possessing varying degrees of torsin activity, and methods of screening and amplifying polynucleotides encoding polypeptide sequences which encode polypeptides having varying degrees of TOR-1, TOR2, OOC-5 TOR-A, and TOR-B activity. Further, the invention relates to methods of reducing protein aggregation, methods of treating diseases that are caused by protein aggregation, methods of screening potential protein-aggregation-reducing products, methods of screening potential therapeutics of diseases caused by protein aggregation, and pharmaceuticals, therapeutics, and kits comprising polynucleotide sequences corresponding to the tor-1, tor-2, ooc-5, DYT1, and DYT2 genes and/or polypeptides having torsin activity.

摘要翻译： 本发明涉及多核苷酸，其包含对应于tor-1，tor-2，ooc-5，DYT1和DYT2基因的多核苷酸序列及其部分，其编码具有不同程度的躯干活性的多肽序列及其部分，以及筛选和 扩增编码多肽序列的多核苷酸，其编码具有不同程度的TOR-1，TOR2，OOC-5TOR-A和TOR-B活性的多肽。 此外，本发明涉及减少蛋白质聚集的方法，治疗由蛋白质聚集引起的疾病的方法，筛选潜在的蛋白质聚集减少产品的方法，筛选由蛋白质聚集引起的疾病的潜在治疗剂的方法以及药物，治疗剂 ，以及包含对应于具有抗转录活性的tor-1，tor-2，ooc-5，DYT1和DYT2基因和/或多肽的多核苷酸序列的试剂盒。

公开(公告)号：US20090111768A1

公开(公告)日：2009-04-30

申请号：US12221826

申请日：2008-08-07

申请人： Guy Caldwell ,  Kim A. Caldwell

发明人： Guy Caldwell ,  Kim A. Caldwell

IPC分类号： A61K31/7088 ,  G01N33/00 ,  C12Q1/26 ,  G01N33/573 ,  G01N33/566 ,  C12Q1/68 ,  C40B30/04 ,  A01K67/027

CPC分类号： G01N33/6896 ,  C07K14/47 ,  C12N9/001 ,  G01N2333/90206

摘要： Polynucleotide molecules and the proteins encoded by the molecules, diagnostic and treatment methods for neurological disorders characterized by protein aggregation are provided. Genes are described herein that affect the misfolding of, and subsequent aggregation of, aggregation-prone proteins such as alpha-synuclein and have implications for the diagnosis and treatment of neurological diseases related to protein aggregation such as Parkinson's disease. Knockdown of expression of the genes described herein using RNAi results in alpha-synuclein protein aggregation in a C. elegans model of protein aggregation. Dopaminergic neuroprotection after overexpression of alpha-synuclein may also be provided by overexpression of proteins. Knowledge of genes relating to protein misfolding and aggregation provides powerful means to develop diagnostic screening methods, mutation analysis and drug design information for the development of novel therapeutic and neuroprotective compounds to treat neurodegenerative diseases such as Parkinson's disease.

摘要翻译： 提供多核苷酸分子和由分子编码的蛋白质，以蛋白质聚集为特征的神经障碍的诊断和治疗方法。 本文描述了影响易聚集的蛋白质例如α-突触核蛋白的错误折叠和随后的聚集的基因，并且涉及诊断和治疗与蛋白质聚集相关的神经疾病如帕金森病。 使用RNAi敲除本文所述基因的表达导致蛋白质聚集的线虫模型中的α-突触核蛋白聚集。 α-突触核蛋白过度表达后的多巴胺能神经保护也可以通过蛋白质的过表达来提供。 关于蛋白质错折叠和聚集相关基因的知识为开发用于治疗神经变性疾病如帕金森病的新型治疗和神经保护化合物开发诊断筛选方法，突变分析和药物设计信息提供了有力手段。

公开(公告)号：US20070204352A1

公开(公告)日：2007-08-30

申请号：US11364612

申请日：2006-02-27

申请人： Guy Caldwell ,  Kim Caldwell

发明人： Guy Caldwell ,  Kim Caldwell

IPC分类号： A01K67/027 ,  G01N33/567

CPC分类号： G01N33/6896 ,  A01K67/0336 ,  A01K2227/703 ,  A01K2267/0318 ,  G01N2500/00

摘要： Polynucleotide molecules and the proteins encoded by the molecules, diagnostic and treatment methods for neurological disorders characterized by protein aggregation are provided. Genes are described herein that affect the misfolding of, and subsequent aggregation of, aggregation-prone proteins such as alpha-synuclein and have implications for the diagnosis and treatment of neurological diseases related to protein aggregation such as Parkinson's disease. Knockdown of expression of the genes described herein using RNAi results in alpha-synuclein protein aggregation in a C. elegans model of protein aggregation. Dopaminergic neuroprotection after exposure to the neurotoxin 6-OHDA or overexpression of alpha-synuclein may also be provided by overexpression of proteins. Knowledge of genes relating to protein misfolding and aggregation provides powerful means to develop diagnostic screening methods, mutation analysis and drug design information for the development of novel therapeutic and neuroprotective compounds to treat neurodegenerative diseases such as Parkinson's disease.

摘要翻译： 提供多核苷酸分子和由分子编码的蛋白质，以蛋白质聚集为特征的神经障碍的诊断和治疗方法。 本文描述了影响易聚集的蛋白质例如α-突触核蛋白的错误折叠和随后的聚集的基因，并且涉及诊断和治疗与蛋白质聚集相关的神经疾病如帕金森病。 使用RNAi敲除本文所述基因的表达导致蛋白质聚集的线虫模型中的α-突触核蛋白聚集。 暴露于神经毒素6-OHDA或α-突触核蛋白的过表达后的多巴胺能神经保护也可以通过蛋白质的过表达来提供。 关于蛋白质错折叠和聚集相关基因的知识为开发用于治疗神经变性疾病如帕金森病的新型治疗和神经保护化合物开发诊断筛选方法，突变分析和药物设计信息提供了有力手段。