Methods for modulating transcription from the amyloid .beta.-protein
precursor (APP) promoter
    12.
    发明授权
    Methods for modulating transcription from the amyloid .beta.-protein precursor (APP) promoter 失效
    调节淀粉样蛋白β-蛋白前体(APP)启动子转录的方法

    公开(公告)号:US5643726A

    公开(公告)日:1997-07-01

    申请号:US339152

    申请日:1994-11-10

    摘要: The application concerns methods for modulating transcription from the amyloid .beta.-protein precursor (APP) promoter. The upstream stimulatory factor (USF) is described as being capable of activating transcription from the APP promoter. Also described are USF binding compounds which are capable of down-regulating expression from the APP promoter. Preferred USF binding compounds are the amyloid precursor-like proteins APLP1 and APLP2. The application further concerns a screening assay for determining which candidate USF binding compounds are capable of causing down-regulation of transcription from the APP promoter.

    摘要翻译: 该应用涉及从淀粉样蛋白β-蛋白前体(APP)启动子调节转录的方法。 上游刺激因子(USF)被描述为能够激活来自APP启动子的转录。 还描述了能够下调APP启动子表达的USF结合化合物。 优选的USF结合化合物是淀粉样前体样蛋白APLP1和APLP2。 该应用还涉及用于确定哪些候选的USF结合化合物能够引起来自APP启动子的转录下调的筛选测定。

    Diagnostic assay for Alzheimer's disease: assessment of Aβ abnormalities
    16.
    发明授权
    Diagnostic assay for Alzheimer's disease: assessment of Aβ abnormalities 失效
    阿尔茨海默病的诊断测定:Abeta异常的评估

    公开(公告)号:US06890727B2

    公开(公告)日:2005-05-10

    申请号:US09425956

    申请日:1999-10-25

    IPC分类号: G01N33/553 G01N33/53

    摘要: The disclosed invention relates to assays for detecting and quantifying Aβ peptide, using solid supports that are coated with heavy metal cations, such as zinc (II) or copper (II) form of a nitriloacetic acid. Further, diagnostic kits are described which are used to carry out the assays of the present invention. An improvement in an assay for detection of Aβ peptide is suggested which comprises forming a heavy metal cation/solid support complex. The preferred heavy metal cations for this improvement are zinc (II) or copper (II) form of a nitriloacetic acid. Finally, methods and kits for bulk purification of Aβ peptides from biological fluids are taught.

    摘要翻译: 所公开的发明涉及使用用重金属阳离子如锌(II)或铜(II)形式的次氮基乙酸涂覆的固体支持物来检测和定量Aβ肽的测定法。 此外,描述了用于进行本发明的测定的诊断试剂盒。 提出了用于检测Abeta肽的测定的改进,其包括形成重金属阳离子/固体支持物复合物。 用于此改进的优选重金属阳离子是次锌乙酸锌(II)或铜(II)形式。 最后,教导了从生物液体中大量净化Abeta肽的方法和试剂盒。

    Purified 20 kDA presenilin 2 C-terminal fragment and methods of screening for compounds that inhibit proteolysis of presenilin 2
    17.
    发明授权
    Purified 20 kDA presenilin 2 C-terminal fragment and methods of screening for compounds that inhibit proteolysis of presenilin 2 失效
    纯化的20kDA早老素2 C-末端片段和筛选抑制早老素蛋白水解的化合物的方法2

    公开(公告)号:US06887983B2

    公开(公告)日:2005-05-03

    申请号:US09065902

    申请日:1998-04-24

    摘要: The present invention relates, in general, to presenilin 2 proteolytic fragments. In particular, the present invention relates to a purified 20 kDa presenilin 2 C-terminal fragment (PS2-CTF); purified nucleic acid molecules coding for the 20 kDa PS2-CTF protein; cells containing the nucleic acid molecules; non-human organisms containing the nucleic acid molecule; antibodies having specific binding affinity to the 20 kDa PS2-CTF; hybridomas containing the antibodies; methods of detecting 20 kDa PS2-CTF in a sample; diagnostic kits; methods for screening compounds that inhibit proteolytic processing of presenilin 2 in a cell, isolated compounds that inhibit proteolytic processing of presenilin 2 in a cell, and a method of inhibiting apoptotic cell death by preventing proteolytic cleavage of presenilin 2 at a cleavage site which generates a 20 kDa C-terminal fragment.

    摘要翻译: 本发明一般涉及早老素2蛋白水解片段。 特别地,本发明涉及纯化的20kDa早老素2 C-末端片段(PS2-CTF); 编码20kDa PS2-CTF蛋白质的纯化核酸分子; 含有核酸分子的细胞; 含有核酸分子的非人体生物体; 对20kDa PS2-CTF具有特异性结合亲和力的抗体; 含有抗体的杂交瘤; 检测样品中20kDa PS2-CTF的方法; 诊断试剂盒 用于筛选抑制细胞中早老素2的蛋白水解加工的化合物的方法,抑制细胞中早老素2的蛋白水解加工的分离的化合物,以及通过在切割位点处阻止早老素2的蛋白水解切割来抑制凋亡细胞死亡的方法, 20 kDa C末端片段。

    &agr;-2- macroglobulin therapies and drug screening methods for Alzheimer's disease.
    19.
    发明授权
    &agr;-2- macroglobulin therapies and drug screening methods for Alzheimer's disease. 失效
    阿尔茨海默氏病的α-2-巨球蛋白治疗和药物筛选方法。

    公开(公告)号:US06472140B1

    公开(公告)日:2002-10-29

    申请号:US09241606

    申请日:1999-02-02

    IPC分类号: C12Q100

    摘要: The disclosed invention relates to the finding that the A2M-2 deletion mutation, which is a predisposing factor for Alzheimer's Disease, leads to the production of altered &agr;2M RNA transcripts and proteins. Based on this finding, the invention provides for new therapeutic agents for AD, including molecules having A&bgr; and low density lipoprotein receptor-related protein (LRP) binding domains, peptides, nucleic acid molecules, antisense oligonucleotides, and viral vectors for gene therapy. In addition, the invention relates to pharmaceutical compositions containing these therapeutic agents, methods of using these therapeutic agents to combat Alzheimer's Disease, and methods of screening for therapeutic agents that can combat Alzheimer's Disease.

    摘要翻译: 所公开的发明涉及A2M-2缺失突变(其是阿尔茨海默病的诱发因子)导致产生改变的α2MRNA转录物和蛋白质的发现。 基于这一发现,本发明提供了用于AD的新治疗剂,包括具有Abeta和低密度脂蛋白受体相关蛋白(LRP)结合结构域的分子,肽,核酸分子,反义寡核苷酸和用于基因治疗的病毒载体。 此外,本发明涉及含有这些治疗剂的药物组合物,使用这些治疗剂来对抗阿尔茨海默氏病的方法,以及筛选可以对抗阿尔茨海默病的治疗剂的方法。