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    • 4. 发明授权
    • Transgenic mice for screening for inhibitors of protein aggregation and methods for making and using them
    • 用于筛选蛋白质聚集抑制剂的转基因小鼠及其制备和使用方法
    • US07795495B2
    • 2010-09-14
    • US11675607
    • 2007-02-15
    • Eliezer MasliahEdward RockensteinMakoto Hashimoto
    • Eliezer MasliahEdward RockensteinMakoto Hashimoto
    • A01K67/027A01K67/00G01N33/00
    • C12N15/8509A01K67/0275A01K67/0276A01K67/0278A01K2207/15A01K2217/00A01K2217/05A01K2217/075A01K2227/105A01K2267/0312A01K2267/0318A61K38/00A61K48/00C07K14/47C07K14/4711C12N2830/008
    • The methodologies of the present invention demonstrate that a critical balance between pro- and anti-amyloidogenic molecules exists that regulates amyloid formation and cell death in Alzheimer's disease and Parkinson's disease. β-Synuclein, the non-amyloidogenic homologue of α-synuclein, is a negative modulator of α-synuclein and Aβ aggregation, having neuroprotective properties against α-synuclein and Aβ neurotoxicity and that β-synuclein and therapeutic agents derived therefrom block amyloidogenesis and neurodegeneration in vivo. The method of the present invention establishes that β-synuclein blocks Aβ aggregation either by direct inhibition of Aβ amyloidogenesis or indirectly via either α-synuclein or its 35 a.a. NAC region, inferring neuroprotective characteristics within the effected cells. The generation of a transgenic mouse line and a cell system overexpressing α-synuclein characterizes the mechanisms by which β-synuclein blocks α-synuclein and Aβ aggregation and that this mechanism offers protection to the cell against amyloid formation as seen in the pathologies of Alzheimer's disease and Parkinson's disease.
    • 本发明的方法证明,存在调节淀粉样蛋白形成和阿尔茨海默病和帕金森病中的细胞死亡的促淀粉样变性分子和抗淀粉样蛋白形成分子之间的关键平衡。 α-突触核蛋白的非淀粉样变性同源物 - 突触核蛋白是α-突触核蛋白和A&bgr的负调节剂; 聚集,对α-突触核蛋白和A&bgr有神经保护作用; 神经毒性以及由此产生的结核分枝杆菌和其衍生的治疗剂在体内阻断淀粉样变性和神经变性。 本发明的方法确定了结核分裂素A和bgr; 通过直接抑制A&bgr的聚集; 淀粉样蛋白发生或间接通过α-突触核蛋白或其35 a.a. NAC区域,推断受影响细胞内的神经保护特征。 转基因小鼠系的产生和过表达α-突触核蛋白的细胞系统的特征在于这样的机制,其中β-突触核蛋白阻断α-突触核蛋白和A&bgr; 并且该机制为阿尔茨海默氏病和帕金森病的病理学中所观察到的针对淀粉样蛋白形成的细胞提供了保护。
    • 6. 发明授权
    • Method for screening for anti-amyloidogenic properties and method for treatment of neurodegenerative disease
    • 筛选抗淀粉样变性的方法和治疗神经变性疾病的方法
    • US07226746B1
    • 2007-06-05
    • US09806842
    • 1999-10-06
    • Eliezer MasliahMakoto HashimotoEdward Rockenstein
    • Eliezer MasliahMakoto HashimotoEdward Rockenstein
    • G01N33/53
    • G01N33/5058G01N2333/47G01N2500/00
    • 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.
    • 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。
    • 10. 发明授权
    • Primer composition for polyolefins
    • 聚烯烃的底漆组合物
    • US5932654A
    • 1999-08-03
    • US971230
    • 1997-11-15
    • Takeshi OgawaKatsuo MiyazakiMakoto Hashimoto
    • Takeshi OgawaKatsuo MiyazakiMakoto Hashimoto
    • C08J7/04C08F255/02C08L23/26C08L23/28C08L51/00C08L51/06C08G63/91
    • C08F255/02C08L51/06
    • The present invention provides a primer composition for polyolefins which has sufficient adhesion to polyolefin base materials and excellent resistance to gasohol and high pressure washing of cars. This primer composition for polyolefins comprises: acid anhydride-modified polypropylene chloride (A), which includes polypropylene chloride moiety (a1) and acid anhydride moiety (a2) as bonded thereto, and has a chlorine content of 19.5 to 20.5 wt %, an acid anhydride moiety content of 0.8 to 1.2 wt %, and a weight-average molecular weight of 30,000 to 36,000; and acryl-modified polypropylene chloride (B), which includes polypropylene chloride moiety (b1) and acrylic polymer chain moiety (b2) as grafted thereon, and has a weight-average molecular weight of 30,000 to 200,000, wherein: polypropylene chloride moiety (b1) has a chlorine content of 20 to 30 wt %; acrylic polymer chain moiety (b2) has a glass transition temperature of 60.degree. C. or higher; and the ratio by weight between moieties (b1) and (b2) is b1/b2 =5/95 to 50/50; wherein the ratio by weight between acid anhydride-modified polypropylene chloride (A) and acryl-modified polypropylene chloride (B) is A/B=90/10 to 20/80.
    • 本发明提供了一种聚烯烃的底漆组合物,其具有对聚烯烃基材的充分粘合性和优异的耐汽油性和耐汽车高压洗涤性能。 该聚烯烃用底漆组合物包括:酸酐改性聚丙烯氯化物(A),其包括聚丙烯氯化物部分(a1)和与其结合的酸酐部分(a2),氯含量为19.5-20.5重量%,酸 酸酐部分含量为0.8〜1.2重量%,重均分子量为30,000〜36,000; 和丙烯酰基改性聚丙烯氯化物(B),其包括聚丙烯氯化物部分(b1)和丙烯酸聚合物链部分(b2),其重均分子量为30,000至200,000,其中:聚丙烯氯化物部分(b1 )的氯含量为20〜30重量%。 丙烯酸聚合物链部分(b2)的玻璃化转变温度为60℃以上; (b1)和(b2)之间的重量比为b1 / b2 = 5/95〜50/50; 其中,酸酐改性聚丙烯氯化物(A)与丙烯酸改性聚丙烯氯化物(B)的重量比为A / B = 90/10〜20/80。