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19 条记录 (耗时 0.022 秒)

    Method of screening a compound for anxiolytic activity in an Apolipoprotein e knockout animal
    1.
    发明授权
    Method of screening a compound for anxiolytic activity in an Apolipoprotein e knockout animal 有权
    在载脂蛋白e敲除动物中筛选化合物抗焦虑活性的方法

    公开(公告)号：US06982361B1

    公开(公告)日：2006-01-03

    申请号：US09512840

    申请日：2000-02-25

    申请人： Jacob Raber ,  Lennart Mucke

    发明人： Jacob Raber ,  Lennart Mucke

    IPC分类号： G01N3/00

    CPC分类号： C12N15/8509 ,  A01K67/0276 ,  A01K2217/075 ,  A01K2227/10 ,  A01K2227/105 ,  A01K2267/03 ,  A61K38/1709

    摘要： Methods and compositions for use in treating anxiety are provided. In the subject methods, an effective amount of an agent having ApoE3 activity is administered to a host suffering from an anxiety, e.g. excessive anxiety, unwanted anxiety, an anxiety disorder, etc. Also provided are methods and compositions for modulating adrenal steroidogenesis and/or release, particularly stress induced adrenal steroidogenesis and/or release, and the hippocampal-pituitary-adrenal (HPA) axis. In these methods, an effective amount of an ApoE activity modulating agent, e.g. an ApoE agonist or antagonist, is administered to the host.

    摘要翻译： 提供了用于治疗焦虑症的方法和组合物。 在本发明的方法中，将有效量的具有ApoE3活性的药剂施用于患有焦虑的宿主，例如， 过度焦虑，不需要的焦虑，焦虑症等。还提供了用于调节肾上腺类固醇生成和/或释放，特别是应激诱发的肾上腺类固醇生成和/或释放以及海马 - 垂体 - 肾上腺（HPA）轴的方法和组合物。 在这些方法中，有效量的ApoE活性调节剂，例如， 给予宿主ApoE激动剂或拮抗剂。

    Method of screening a compound for anxiolytic activity in an apolipoprotein E knockout animal
    3.
    发明申请
    Method of screening a compound for anxiolytic activity in an apolipoprotein E knockout animal 审中-公开
    在载脂蛋白E敲除动物中筛选化合物抗焦虑活性的方法

    公开(公告)号：US20050245450A1

    公开(公告)日：2005-11-03

    申请号：US11175779

    申请日：2005-07-05

    申请人： Jacob Raber ,  Lennart Mucke

    发明人： Jacob Raber ,  Lennart Mucke

    IPC分类号： A01K67/027 ,  A61K38/17 ,  A61K48/00 ,  C12N15/85

    CPC分类号： C12N15/8509 ,  A01K67/0276 ,  A01K2217/075 ,  A01K2227/10 ,  A01K2227/105 ,  A01K2267/03 ,  A61K38/1709

    摘要： Methods and compositions for use in treating anxiety are provided. In the subject methods, an effective amount of an agent having ApoE3 activity is administered to a host suffering from an anxiety, e.g. excessive anxiety, unwanted anxiety, an anxiety disorder, etc. Also provided are methods and compositions for modulating adrenal steroidogenesis and/or release, particularly stress induced adrenal steroidogenesis and/or release, and the hippocampal-pituitary-adrenal (HPA) axis. In these methods, an effective amount of an ApoE activity modulating agent, e.g. an ApoE agonist or antagonist, is administered to the host.

    摘要翻译： 提供了用于治疗焦虑症的方法和组合物。 在本发明的方法中，将有效量的具有ApoE3活性的药剂施用于患有焦虑的宿主，例如， 过度焦虑，不需要的焦虑，焦虑症等。还提供了用于调节肾上腺类固醇生成和/或释放，特别是应激诱发的肾上腺类固醇生成和/或释放以及海马 - 垂体 - 肾上腺（HPA）轴的方法和组合物。 在这些方法中，有效量的ApoE活性调节剂，例如， 给予宿主ApoE激动剂或拮抗剂。

    METHODS AND COMPOSITIONS FOR REDUCING AMYLOID BETA LEVELS
    4.
    发明申请
    METHODS AND COMPOSITIONS FOR REDUCING AMYLOID BETA LEVELS 有权
    降低AMYLOID BETA水平的方法和组合物

    公开(公告)号：US20100040612A1

    公开(公告)日：2010-02-18

    申请号：US12447241

    申请日：2007-11-15

    申请人： Li Gan ,  Lennart Mucke

    发明人： Li Gan ,  Lennart Mucke

    IPC分类号： A61K39/395 ,  C12N5/00 ,  C12Q1/37 ,  A61K31/7052 ,  A61K38/16 ,  A61P25/28 ,  A61K38/02 ,  A61P25/00

    CPC分类号： C12Q1/37 ,  A61K31/7052 ,  A61K38/00 ,  A61K38/55 ,  A61K39/3955 ,  C07K16/38 ,  C12N15/1136 ,  C12N15/1137 ,  C12N2310/14 ,  C12N2310/531 ,  C12N2330/51 ,  C12Q1/68 ,  G01N33/6896

    摘要： The present invention provides methods for reducing the level of amyloid beta protein in a cell or tissue, the methods generally involving contacting the cell or tissue with an agent that reduces cystatin C levels and/or activity. The present invention provides methods for treating Alzheimer's disease (AD), and methods for treating cerebral angiopathy, in an individual, the methods generally involving administering to an individual having AD a therapeutically effective amount of an agent that reduces cystatin C levels and/or activity. The present invention further provides methods for identifying an agent that reduces cystatin C levels and/or activity.

    摘要翻译： 本发明提供降低细胞或组织中淀粉样蛋白β蛋白水平的方法，所述方法通常涉及使细胞或组织与降低半胱氨酸蛋白酶抑制剂C水平和/或活性的试剂接触。 本发明提供了治疗阿尔茨海默氏病（AD）的方法和个体治疗脑血管病的方法，通常涉及向患有AD的个体施用治疗有效量的减少半胱氨酸蛋白酶抑制剂C水平和/或活性的药物的方法 。 本发明进一步提供了用于鉴定降低半胱氨酸蛋白酶抑制剂C水平和/或活性的试剂的方法。

    Methods of detecting neurological disorders
    6.
    发明授权
    Methods of detecting neurological disorders 有权
    检测神经系统疾病的方法

    公开(公告)号：US07297836B2

    公开(公告)日：2007-11-20

    申请号：US10809777

    申请日：2004-03-24

    申请人： Lennart Mucke ,  Jorge J. Palop

    发明人： Lennart Mucke ,  Jorge J. Palop

    IPC分类号： G01N33/00 ,  C12N15/00

    CPC分类号： A01K67/0275 ,  A01K2217/05 ,  A01K2227/105 ,  A01K2267/0312 ,  C07K14/4711 ,  C12N2810/851 ,  G01N33/6896 ,  G01N2333/4709 ,  G01N2333/4727 ,  G01N2800/28 ,  G01N2800/2821

    摘要： The present invention provides methods of detecting an amyloid peptide-related neurological disorder in an individual; and methods for staging an amyloid peptide-related neurological disorder in an individual. The methods involve detecting a level of a calcium-responsive gene product, such as calbindin, in a hippocampal neuron, especially a granule cell of the dentate gyrus. The invention further provides identifying an agent that treats an amyloid peptide-related neurological disorder, as well as agents identified by the methods.

    摘要翻译： 本发明提供了检测个体中淀粉样蛋白肽相关神经障碍的方法; 以及在个体中分期淀粉样蛋白肽相关的神经障碍的方法。 所述方法包括检测海马神经元，特别是齿状回的颗粒细胞中钙响应性基因产物如钙结合蛋白的水平。 本发明进一步提供鉴定治疗淀粉样蛋白肽相关神经障碍的药物以及通过该方法鉴定的药剂。

    Human α synuclein expressing transgenic mice
    7.
    发明授权
    Human α synuclein expressing transgenic mice 有权
    人α突触核蛋白表达转基因小鼠

    公开(公告)号：US07459601B2

    公开(公告)日：2008-12-02

    申请号：US10853774

    申请日：2004-05-24

    申请人： Eliezer Masliah ,  Makoto Hashimoto ,  Edward Rockenstein ,  Lennart Mucke

    发明人： Eliezer Masliah ,  Makoto Hashimoto ,  Edward Rockenstein ,  Lennart Mucke

    IPC分类号： A01K67/00 ,  A01K67/033 ,  A01K67/027 ,  C12N5/06 ,  C12N5/10

    CPC分类号： G01N33/6896 ,  A61K38/1709 ,  C07K16/18

    摘要： In methods for screening treatments for, and treatment of, neurodegenerative diseases, aggregation in neurons of NACP/α-synuclein is measured and expression of a non-amyloidogenic protein is stimulated in order to reduce the level aggregration. For purposes of screening agents for treatment of neurodegenerative disease, oxidative stress in the neuronal cells is stimulated by introducing a mixture of metal-ions and hydrogen peroxide. Examples of appropriate metals include iron, aluminum, and copper. After introduction of the agent under evaluation for stimulation of expression of non-amyloidogenic protein, the effectiveness is measured by testing for a decrease in the level of aggregation of NACP/α-synuclein. In an exemplary embodiment, the non-amyloidogenic protein is β-synuclein. The aggregation of NACP/α-synuclein is dependent upon the concentration of metal ions in the neuronal cells. In addition, the presence of chelating agents appears to modulate the build-up of NACP/α-synuclein aggregates which are responsible for synaptic and neuronal dysfunction.

    摘要翻译： 在用于筛选神经变性疾病的治疗和治疗方法中，测量NACP /α-突触核蛋白的神经元中的聚集，并刺激非淀粉样蛋白生成蛋白的表达以降低水平聚集。 为了筛选用于治疗神经变性疾病的药剂，通过引入金属离子和过氧化氢的混合物刺激神经元细胞中的氧化应激。 合适金属的实例包括铁，铝和铜。 在引入用于刺激非淀粉样蛋白形成蛋白表达的试剂之后，通过测试NACP /α-突触核蛋白的聚集水平的降低来测量有效性。 在一个示例性实施方案中，非淀粉样蛋白生成蛋白是β-突触核蛋白。 NACP /α-突触核蛋白的聚集取决于神经元细胞中金属离子的浓度。 此外，螯合剂的存在似乎调节负责突触和神经元功能障碍的NACP /α-突触核蛋白聚集体的积聚。

    Transgenic mice expressing human APP and TGF-&bgr; demonstrate cerebrovascular amyloid deposits
    8.
    发明授权
    Transgenic mice expressing human APP and TGF-&bgr; demonstrate cerebrovascular amyloid deposits 有权
    表达人APP和TGF-β的转基因小鼠表现出脑血管淀粉样蛋白沉积

    公开(公告)号：US06455757B1

    公开(公告)日：2002-09-24

    申请号：US09262519

    申请日：1999-03-04

    申请人： Lennart Mucke ,  Tony Wyss-Coray ,  Eliezer Masliah

    发明人： Lennart Mucke ,  Tony Wyss-Coray ,  Eliezer Masliah

    IPC分类号： A01K6700

    CPC分类号： C12N15/8509 ,  A01K67/0275 ,  A01K67/0278 ,  A01K2207/15 ,  A01K2217/00 ,  A01K2217/05 ,  A01K2227/105 ,  A01K2267/0312 ,  A01K2267/0318 ,  C12N2830/008

    摘要： The present invention features non-human transgenic animal models for Alzheimer's disease (AD) and CAA, wherein the transgenic animal is characterized by 1) expression of bioactive transforming growth factor-&bgr;1 (TGF-&bgr;1) or 2) both expression of bioactive TGF-&bgr;1 and expression of a human amyloid &bgr; precursor protein (APP) gene product. The transgenic animals may be either homozygous or heterozygous for these alterations. Bigenic animals are further characterized by development of AD-associated and/or CAA-associated pathology within about two to three months of age, and at about twelve months of age are characterized by a reduced number of neuritic plaques relative to singly transgenic animals. The invention also features methods of screening for biologically active agents that facilitate reduction of &bgr;-amyloid deposits in vivo and methods for facilitating reduction of formation of neuritic plaques in a subject susceptible to AD.

    摘要翻译： 本发明的特征在于用于阿尔茨海默氏病（AD）和CAA的非人转基因动物模型，其中转基因动物的特征在于1）生物活性转化生长因子-β1（TGF-β1）的表达或2）生物活性TGF- β1和人淀粉样蛋白β前体蛋白（APP）基因产物的表达。 对于这些改变，转基因动物可以是纯合的或杂合的。 本发型动物的进一步特征在于在约2-3个月龄内发展与AD相关和/或CAA相关的病理学，并且在约12个月龄时，其特征在于相对于单一转基因动物数量减少的神经炎斑块。 本发明还涉及筛选促进体内β-淀粉样蛋白沉积物减少的生物活性剂的方法以及用于促进减轻易受AD影响的受试者的神经炎斑块形成的方法。

    Methods and compositions for reducing amyloid beta levels
    10.
    发明授权
    Methods and compositions for reducing amyloid beta levels 有权
    降低淀粉样蛋白β水平的方法和组合物

    公开(公告)号：US07951367B2

    公开(公告)日：2011-05-31

    申请号：US11985601

    申请日：2007-11-15

    申请人： Li Gan ,  Lennart Mucke ,  Erik Roberson ,  Sarah Mueller-Steiner

    发明人： Li Gan ,  Lennart Mucke ,  Erik Roberson ,  Sarah Mueller-Steiner

    IPC分类号： A61K38/43

    CPC分类号： C12Y304/22001 ,  A61K38/4813 ,  C12N9/641 ,  C12N2799/022 ,  C12N2799/027 ,  C12N2799/06

    摘要： The present invention provides a method of increasing cathepsin B-induced cleavage of amyloid-β (Aβ) peptide in a cell or tissue, the method generally involving contacting the cell or tissue with an agent that increases the level of cathepsin B in the cell or tissue. The present invention further provides variant cathepsin B polypeptides that are resistant to inhibition by a cysteine protease inhibitor; as well as nucleic acids encoding the variants, and host cells comprising the nucleic acids.

    摘要翻译： 本发明提供了一种增加组织蛋白酶B诱导的淀粉样蛋白切割的方法。 （A＆bgr））肽，所述方法通常涉及使细胞或组织与增加细胞或组织中组织蛋白酶B水平的试剂接触。 本发明进一步提供对半胱氨酸蛋白酶抑制剂具有抑制作用的变体组织蛋白酶B多肽; 以及编码变体的核酸，以及包含核酸的宿主细胞。