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    Neurofibrillary labels
    34.
    发明申请
    Neurofibrillary labels 有权
    神经原纤维标签

    公开(公告)号：US20080219929A1

    公开(公告)日：2008-09-11

    申请号：US12071693

    申请日：2008-02-25

    申请人： Claude Michel Wischik ,  Charles Robert Harrington ,  Janet Elizabeth Rickard ,  David Horsley

    发明人： Claude Michel Wischik ,  Charles Robert Harrington ,  Janet Elizabeth Rickard ,  David Horsley

    IPC分类号： A61K49/00 ,  C07D277/62

    CPC分类号： C07D417/12 ,  C07D277/66 ,  C07D279/20 ,  G01N33/583 ,  G01N33/6896

    摘要： A method for determining the Braak stage of neurofibrillary degeneration associated with a tauopathy in a subject having neurofibrillary degeneration is disclosed. The method comprises the steps of (i) administering to the subject a conjugated, chelated or detectable chemical group-associated ligand that labels aggregated paired helical filament (PHF) tau protein and is capable of crossing the blood brain barrier; (ii) determining the presence and\or amount of ligand bound to extracellular aggregated PHF tau in the medial temporal lobe of the brain of the subject, and (iii) correlating the result of the determination made in (ii) with the extent of neurofibrillary degeneration in the subject. Preferred ligands include sulphonated-benzothiazole-like compounds and diamonophenothiazines.

    摘要翻译： 公开了一种用于确定与具有神经原纤维变性的受试者中与tau蛋白病相关的神经原纤维变性的Braak阶段的方法。 该方法包括以下步骤：（i）向受试者施用标记聚集的成对螺旋丝（PHF）tau蛋白并能够穿过血脑屏障的共轭，螯合或可检测的化学基团相关配体; （ii）确定与受试者脑内侧颞叶中细胞外聚集的PHF tau结合的配体的存在和/或数量，以及（iii）将（ii）中确定的测定结果与神经原纤维的程度相关联 主题变性 优选的配体包括磺化苯并噻唑类化合物和二氨基吩噻嗪。

    Materials and methods relating to protein aggregation in neurodegenerative disease
    35.
    发明授权
    Materials and methods relating to protein aggregation in neurodegenerative disease 有权
    与神经退行性疾病中的蛋白质聚集相关的材料和方法

    公开(公告)号：US07335505B2

    公开(公告)日：2008-02-26

    申请号：US10451782

    申请日：2002-01-15

    申请人： Claude Michel Wischik ,  David Horsley ,  Janet Elizabeth Rickard ,  Charles Robert Harrington

    发明人： Claude Michel Wischik ,  David Horsley ,  Janet Elizabeth Rickard ,  Charles Robert Harrington

    IPC分类号： C12M1/20 ,  C12N1/14 ,  C12N5/06 ,  G01N33/53 ,  G01N33/567 ,  C12Q1/02 ,  A01N63/00 ,  A01N39/00 ,  A61K48/00

    CPC分类号： G01N33/6896 ,  A61K31/00 ,  A61K31/5415

    摘要： The present invention provides methods of proteolytically converting a precursor protein (e.g. tau) to a product fragment (e.g., a 12 kd fragment) in a stable cell line, wherein the precursor protein is associated with a disease state in which the precursor protein aggregates pathologically (e.g. a tauopathy), and the methods comprise: (a) providing a stable cell line transfected with nucleic acid encoding: (i) a template fragment of the precursor protein such that the template fragment is constitutively expressed in the cell at a level which is not toxic to the cell; and (ii) the precursor protein, which protein is inducibly expressed in the cell in response to a stimulus, whereby interaction of the template fragment with the precursor protein causes a conformational change in the precursor protein such as to cause aggregation and proteolytic processing of the precursor protein to the product fragment. The method is preferably used to screen for modulators of the aggregation process by monitoring production (or modulation of production) of the product band or bands. Also provided are materials for used in the assays, plus medicaments, and related uses and processes, based on compounds which show high activity in the assay of the invention e.g. reduced diaminophenothiazines.

    摘要翻译： 本发明提供了在稳定细胞系中将前体蛋白质（例如tau）蛋白水解转化成产物片段（例如，12kd片段）的方法，其中前体蛋白质与其中前体蛋白质在病理学上聚集的疾病状态相关联 （例如，tau蛋白病），并且所述方法包括：（a）提供用核酸转染的稳定的细胞系，编码：（i）前体蛋白的模板片段，使得模板片段在细胞中以 对细胞无毒性; 和（ii）前体蛋白质，该蛋白质响应于刺激而在细胞中可诱导表达，由此模板片段与前体蛋白质的相互作用导致前体蛋白质的构象变化，从而导致蛋白质的聚集和蛋白水解加工 前体蛋白到产物片段。 该方法优选用于通过监测产品带或带的生产（或调制生产）来筛选聚集过程的调制器。 还提供了用于测定中的材料，以及基于在本发明的测定中显示高活性的化合物的药物以及相关用途和方法，例如。 还原二氨基吩噻嗪。