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    Abnormalities of Phosphatase 2A (PP2A) for Diagnosis and Treatment of Alzheimer's Disease
    2.
    发明申请
    Abnormalities of Phosphatase 2A (PP2A) for Diagnosis and Treatment of Alzheimer's Disease 审中-公开
    磷酸酶2A（PP2A）用于阿尔茨海默病诊断和治疗的异常

    公开(公告)号：US20090029355A1

    公开(公告)日：2009-01-29

    申请号：US11660868

    申请日：2004-11-15

    申请人： Wei-Qin Zhao ,  Daniel L. Alkon

    发明人： Wei-Qin Zhao ,  Daniel L. Alkon

    IPC分类号： C12Q1/68 ,  C12Q1/42 ,  G01N33/53 ,  C07K16/00

    CPC分类号： C12Q1/6883 ,  C12Q2600/136 ,  C12Q2600/158 ,  G01N33/6896

    摘要： This invention relates to methods of diagnosing Alzheimer's disease and methods of screening for compounds for the treatment or prevention of Alzheimer's disease. The methods are based upon newly discovered differences in protein phosphatase 2A (PP2A) function and related molecular events in Alzheimer's disease cells compared to control cells. In one embodiment, differences in basal PP2A gene expression in Alzheimer's cells are compared to controls. In another embodiment differences in PP2A protein and enzyme activity are compared in test and control cells. In another embodiment differences in response to substances that inhibit PP2A function are compared. Still another embodiment detects differences in the subcellular distribution of phosphorylated Erk1/2, a substrate of PP2A, in normal and Alzheimer's disease cells. The detection of Alzheimer's disease-specific differences in PP2A function and related events in peripheral tissues provides the basis for highly practical and efficient tests and diagnostic test kits for the early diagnosis of Alzheimer's disease, as well as providing a biochemical basis for identifying therapeutic targets for drug development.

    摘要翻译： 本发明涉及诊断阿尔茨海默病的方法和筛选用于治疗或预防阿尔茨海默病的化合物的方法。 该方法基于新发现的蛋白磷酸酶2A（PP2A）功能和阿尔茨海默病细胞相关分子事件与对照细胞相比的差异。 在一个实施方案中，将阿尔茨海默氏病细胞中基础PP2A基因表达的差异与对照进行比较。 在另一个实施方案中，在测试和对照细胞中比较了PP2A蛋白质和酶活性的差异。 在另一个实施方案中，比较了抑制PP2A功能的物质的反应差异。 另一个实施方案检测正常和阿尔茨海默氏病细胞中磷酸化Erk1 / 2（PP2A底物）的亚细胞分布的差异。 检测外周组织中PP2A功能和相关事件中的阿尔茨海默病特异性差异为高龄实用和有效的测试和诊断试剂盒提供了基础，用于早期诊断阿尔茨海默氏病，并为确定治疗靶点提供了生物化学依据 药物开发。

    Controlling attention and memory by altering neuronal carbonic anhydrase activity
    5.
    发明授权
    Controlling attention and memory by altering neuronal carbonic anhydrase activity 失效

    公开(公告)号：US06552053B2

    公开(公告)日：2003-04-22

    申请号：US09875283

    申请日：2001-06-07

    申请人： Miao-Kun Sun ,  Daniel L. Alkon ,  Wei-Qin Zhao

    发明人： Miao-Kun Sun ,  Daniel L. Alkon ,  Wei-Qin Zhao

    IPC分类号： A61K3141

    CPC分类号： A61K31/00 ,  A61K31/433

    摘要： The invention provides a method for modulating attentive cognition comprising administering a compound that alters intraneuronal carbonic anhydrase activity thereby affecting establishment of a theta rhythm. The metabolic pathway of the compound preferably involves bicarbonate-mediated GABAergic depolarization. The term “attentive cognition” is meant to encompass memory formation, learning, spatial memory, and attention. The modulating may be stimulating, or the compound may have the multiple effects of inhibiting intraneuronal carbonic anhydrase activity, establishment of a theta rhythm, and memory acquisition. The invention further provides a method of modulating memory and attention comprising switching theta rhythm on and off, the switching comprising potentiating or inhibiting intraneuronal carbonic anhydrase activity.

    Compositions and methods for the enhancement of soluble amyloid beta oligomer (ADDL) uptake and clearance
    7.
    发明申请
    Compositions and methods for the enhancement of soluble amyloid beta oligomer (ADDL) uptake and clearance 有权
    用于增强可溶性淀粉样蛋白β寡聚物（ADDL）吸收和清除的组合物和方法

    公开(公告)号：US20070264669A1

    公开(公告)日：2007-11-15

    申请号：US11747324

    申请日：2007-05-11

    申请人： Wei-Qin Zhao ,  Grant Krafft ,  William Klein

    发明人： Wei-Qin Zhao ,  Grant Krafft ,  William Klein

    IPC分类号： G01N33/53 ,  A61K38/28

    CPC分类号： G01N33/74 ,  A61K38/28 ,  G01N33/5008 ,  G01N2500/00

    摘要： The present invention relates to methods for enhancing the cellular uptake and clearance of soluble oligomeric Aβ peptide assemblies from the environment surrounding both neuronal and non-neuronal cells. Oligomeric Aβ peptide assembly uptake and clearance is achieved via an agent that enhances insulin receptor signaling. Such ADDL uptake enhancers represent effective anti-ADDL therapeutics for use in the therapeutic treatment and/or prophylactic treatment of diseases including Alzheimer's disease, Down's syndrome, and the like, in which compromised nerve cell function is linked to the formation and/or the activity of soluble oligomeric Aβ peptide assemblies, also known as ADDLs, and ADDL-related assemblies.

    摘要翻译： 本发明涉及从神经元和非神经元细胞周围的环境中增强可溶性寡聚Aβ肽组件的细胞吸收和清除的方法。 通过增强胰岛素受体信号传导的药物来实现低聚Abeta肽组装体摄取和清除。 这种ADDL摄取增强剂代表用于治疗性治疗和/或预防性治疗包括阿尔茨海默氏病，唐氏综合症等的疾病的有效的抗ADDL治疗剂，其中受损的神经细胞功能与形成和/或活性相关 的可溶性低聚Abeta肽组件，也称为ADDL和ADDL相关组件。

    Compositions and methods for the enhancement of soluble amyloid beta oligomer (ADDL) uptake and clearance
    9.
    发明授权
    Compositions and methods for the enhancement of soluble amyloid beta oligomer (ADDL) uptake and clearance 有权
    用于增强可溶性淀粉样蛋白β寡聚物（ADDL）吸收和清除的组合物和方法

    公开(公告)号：US07964359B2

    公开(公告)日：2011-06-21

    申请号：US11747324

    申请日：2007-05-11

    申请人： Wei-Qin Zhao ,  Grant A. Krafft ,  William L. Klein

    发明人： Wei-Qin Zhao ,  Grant A. Krafft ,  William L. Klein

    IPC分类号： G01N33/53 ,  A61K38/28

    CPC分类号： G01N33/74 ,  A61K38/28 ,  G01N33/5008 ,  G01N2500/00

    摘要： The present invention relates to methods for enhancing the cellular uptake and clearance of soluble oligomeric Aβ peptide assemblies from the environment surrounding both neuronal and non-neuronal cells. Oligomeric Aβ peptide assembly uptake and clearance is achieved via an agent that enhances insulin receptor signaling. Such ADDL uptake enhancers represent effective anti-ADDL therapeutics for use in the therapeutic treatment and/or prophylactic treatment of diseases including Alzheimer's disease, Down's syndrome, and the like, in which compromised nerve cell function is linked to the formation and/or the activity of soluble oligomeric Aβ peptide assemblies, also known as ADDLs, and ADDL-related assemblies.

    摘要翻译： 本发明涉及增强可溶性寡聚A和Bgr的细胞吸收和清除的方法。 从神经元和非神经元细胞周围的环境的肽组件。 低聚物 通过增强胰岛素受体信号传导的药物实现肽组装摄取和清除。 这种ADDL摄取增强剂代表用于治疗性治疗和/或预防性治疗包括阿尔茨海默氏病，唐氏综合症等的疾病的有效的抗ADDL治疗剂，其中受损的神经细胞功能与形成和/或活性相关 的可溶性低聚物A＆bgr; 肽组件，也称为ADDL和ADDL相关的组件。