公开(公告)号：US20050209173A1

公开(公告)日：2005-09-22

申请号：US10901848

申请日：2004-07-28

申请人： Isabella Graef ,  Gerald Crabtree ,  Jason Gestwicki

发明人： Isabella Graef ,  Gerald Crabtree ,  Jason Gestwicki

IPC分类号： A61K20060101 ,  A61K31/4745 ,  A61K31/5415 ,  A61K31/655 ,  A61K31/7076 ,  A61K47/48 ,  C12Q1/00

CPC分类号： A61K31/4745 ,  A61K31/5415 ,  A61K31/655 ,  A61K31/7076 ,  A61K47/54

摘要： Methods and compositions are provided for reducing aggregation of neurodegenerative proteins associated with neurotoxicity or other proteins. The compounds comprise a first domain or targeting element for binding to the target proteins linked to a second domain or recruiting element that binds to an aggregation inhibiting protein, e.g. a prolyl isomerase. By associating the aggregating forming proteins or neuronal cells under conditions where aggregating proteins are produced with the compound and the aggregation inhibiting protein, aggregation is reduced. The subject agents can be used in assays, investigating the etiology of the neuronal diseases and for prophylaxis and therapy.

摘要翻译： 提供了用于减少与神经毒性相关的神经变性蛋白质的聚集或其它蛋白质的方法和组合物。 所述化合物包含用于结合靶向蛋白质的第一结构域或靶向元件，所述靶蛋白与结合至聚集抑制蛋白质的第二结构域或募集元件连接。 脯氨酰异构酶。 通过在与化合物和聚集抑制蛋白质产生聚集蛋白质的条件下缔合形成蛋白质或神经元细胞，聚集减少。 主题试剂可用于测定，研究神经元疾病的病因以及预防和治疗。

公开(公告)号：US20050014680A1

公开(公告)日：2005-01-20

申请号：US10824939

申请日：2004-04-15

申请人： Gerald Crabtree ,  Isabella Graef ,  Marc Lavigne

发明人： Gerald Crabtree ,  Isabella Graef ,  Marc Lavigne

IPC分类号： A61K38/18 ,  A61K38/46 ,  G01N33/74 ,  A61K38/28

CPC分类号： G01N33/74 ,  A61K38/18 ,  A61K38/185 ,  A61K38/465 ,  C12Y301/03016 ,  G01N2500/10 ,  Y02A50/401 ,  Y02A50/57

摘要： Pharmaceutical compositions of NF-AT agonists may be used to promote nerve regeneration or to reduce or inhibit secondary nerve degeneration which may otherwise follow primary CNS or PNS injury, e.g., trauma (e.g., blunt trauma, penetrating trauma), compression [e.g., compression due to tendons and/or inflamed synovial membrane such as in carpal tunnel syndrome], bones [for instance sciatica], or growths [benign or cancerous, including growth of the nerves themselves or of surrounding tissue]) hemorrhagic stroke, ischemic stroke or damages caused by surgery such as tumor excision. In certain embodiments, NF-AT agonists may be used to treat spinal cord injuries and promote nerve grafts.

摘要翻译： NF-AT激动剂的药物组合物可用于促进神经再生或减少或抑制继发性神经变性，否则可能会继发于原发性CNS或PNS损伤，例如创伤（例如钝性创伤，穿透性创伤），压迫 由于肌腱和/或发炎滑膜如腕管综合征]，骨骼（例如坐骨神经痛）或生长[良性或癌性，包括神经本身或周围组织的生长]）出血性中风，缺血性卒中或损伤 引起手术如肿瘤切除。 在某些实施方案中，NF-AT激动剂可用于治疗脊髓损伤并促进神经移植物。

公开(公告)号：US07323439B2

公开(公告)日：2008-01-29

申请号：US09960708

申请日：2001-09-19

申请人： Gerald R. Crabtree ,  Isabella Graef ,  Feng Chen

发明人： Gerald R. Crabtree ,  Isabella Graef ,  Feng Chen

IPC分类号： A61K31/00 ,  A61K31/70 ,  C12N5/00

CPC分类号： A61K38/13 ,  G01N33/5011 ,  G01N33/6872 ,  G01N2500/02

摘要： Methods and compositions for modulating angiogenesis in a host are provided. In the subject methods, an effective amount of Ca2+/calcineurin/NF-ATc signaling pathway modulatory agent is administered to the host. In many embodiments, the Ca2+/calcineurin/NF-ATc signaling pathway modulatory agent is an NF-ATc antagonist, e.g., in those embodiments of inhibiting angiogenesis. The subject methods find use in a variety of different applications, including the inhibition of tumor growth and the treatment of disease conditions characterized by tumor presence. Also provided are methods of screening for agents that inhibit angiogenesis by modulating the Ca2+/calcineurin/NF-ATc signaling pathway.

摘要翻译： 提供了用于调节宿主中血管生成的方法和组合物。 在本方法中，向宿主施用有效量的Ca 2+ /钙调神经磷酸酶/ NF-ATc信号通路调节剂。 在许多实施方案中，Ca 2+ /钙调神经磷酸酶/ NF-ATc信号通路调节剂是NF-ATc拮抗剂，例如在抑制血管生成的那些实施方案中。 本发明的方法可用于各种不同的应用，包括抑制肿瘤生长和治疗以肿瘤存在为特征的疾病状况。 还提供了通过调节Ca 2+ /钙调神经磷酸酶/ NF-ATc信号通路来筛选抑制血管生成的药剂的方法。