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    • 6. 发明授权
    • Transgenic animals, cell lines derived therefrom, and methods for screening for anti-amyloidogenic agents
    • 转基因动物,由其衍生的细胞系,以及筛选抗淀粉样变性剂的方法
    • US07276643B2
    • 2007-10-02
    • US10204337
    • 2001-02-20
    • Eliezer MasliahEdward RockensteinHersey Mallory, legal representative
    • Margaret Mallory, deceased
    • A01K67/027G01N33/00C12N5/02
    • 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。 β-共核蛋白是α-突触核蛋白的非淀粉样变性同源物,是α-突触核蛋白和Abeta聚集的负调节剂,具有针对α-突触核蛋白和Abeta神经毒性的神经保护性质,并且β-突触核蛋白和衍生自其的治疗剂阻断淀粉样变性和神经变性 体内。 本发明的方法确定了β-突触核蛋白通过直接抑制Aβ淀粉样变性或间接通过α-突触核蛋白或其αααα阻断Aβ聚集。 NAC区域,推断受影响细胞内的神经保护特征。 转基因小鼠系和过表达α-突触核蛋白的细胞系统的产生表征β-突触核蛋白阻断α-突触核蛋白和Abeta聚集的机制,并且该机制为细胞抵抗淀粉样蛋白形成提供了保护,如阿尔茨海默病病理学 和帕金森病。
    • 9. 发明授权
    • Compounds for reversing and inhibiting protein aggregation, and methods for making and using them
    • 用于逆转和抑制蛋白质聚集的化合物,以及制备和使用它们的方法
    • US08946165B2
    • 2015-02-03
    • US13119400
    • 2009-09-29
    • Eliezer MasliahBrian SpencerEdward RockensteinRobert Marr
    • Eliezer MasliahBrian SpencerEdward RockensteinRobert Marr
    • A61K38/00C07K14/47C07K19/00
    • C07K14/4711A61K38/00C07K19/00
    • The invention provides compositions for increasing the clearance of protein aggregates, and pharmaceutical compositions comprising them, and methods for making and using them, including methods for accelerating protein aggregate clearance in the CNS, e.g., for treating diseases that are characterized by protein aggregation—including some degenerative neurological diseases such as Parkinson's disease. In one aspect, the compositions of the invention specifically target synuclein, beta-amyloid and/or tau protein aggregates, and the methods of the invention can be used to specifically prevent, reverse, slow or inhibit synuclein, beta-amyloid and/or tau protein aggregation. In alternative embodiments, the compositions and methods of the invention, are used to treat, prevent, reverse (partially or completely) or ameliorate (including slowing the progression of) degenerative neurological diseases related to or caused by protein aggregation, e.g., synuclein, beta-amyloid and/or tau protein aggregation. In one aspect, compositions and methods of this invention are used to treat, prevent or ameliorate (including slowing the progression of) Parkinson's disease, fronto-temporal dementia (FTD), Alzheimer's Disease (AD), Lewy body disease (LBD) and Multiple system atrophy (MSA).
    • 本发明提供了用于增加蛋白质聚集体清除率的组合物,以及包含它们的药物组合物,以及用于制备和使用它们的方法,包括用于加速CNS中的蛋白质聚集体清除的方法,例如用于治疗以蛋白质聚集为特征的疾病 一些退行性神经系统疾病如帕金森病。 在一个方面,本发明的组合物特异性靶向突触核蛋白,β-淀粉样蛋白和/或tau蛋白聚集体,并且本发明的方法可用于特异性地预防,逆转,减缓或抑制突触核蛋白,β-淀粉样蛋白和/或tau 蛋白质聚集。 在替代实施方案中,本发明的组合物和方法用于治疗,预防,逆转(部分或完全)或改善(包括减缓进展)与蛋白质聚集相关或由其引起的退行性神经疾病,例如突触核蛋白,β - 淀粉样蛋白和/或tau蛋白聚集。 一方面,本发明的组合物和方法用于治疗,预防或改善(包括减缓帕金森氏病,颞叶性痴呆(FTD),阿尔茨海默病(AD),路易体病(LBD)和多发性硬化症 系统萎缩(MSA)。