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    • 9. 发明授权
    • Presenilin-deficient mouse model of age-dependent neurodegeneration and cognitive loss
    • 早老素缺陷小鼠模型的年龄依赖性神经变性和认知损失
    • US07271313B2
    • 2007-09-18
    • US10409672
    • 2003-04-09
    • Jie Shen
    • Jie Shen
    • A01K67/027C12N15/00
    • A01K67/0276A01K2217/075A01K2227/105A01K2267/0312C07K14/4711C12N15/8509C12N2800/30
    • The present invention is directed to recombinantly engineered mice that are deficient in the expression of both presenilin-1 and presenilin-2. The mice exhibit characteristics of age-dependent cognitive impairments and neurodegeneration similar to those seen in Alzheimer's disease patients. This presenilin-deficient mouse model can be used to screen compounds capable of slowing, preventing or reversing the progression of cognitive impairments and neurodegeneration. The invention is also directed to the development of treatments for Alzheimer's disease based on augmentation or restoration of presenilin function in the brain. On the basis of the findings described herein, the invention is further directed to the development of assays to detect functional presenilin deficiency in human individuals, preferably through analysis of presenilin substrates, which may provide biomarkers useful in the diagnosis of Alzheimer's disease.
    • 本发明涉及缺乏早老素-1和早老蛋白-2的表达的重组工程小鼠。 老鼠显示与老年痴呆症患者相似的年龄依赖性认知障碍和神经变性的特征。 这种早老素缺乏型小鼠模型可用于筛选能够减缓,预防或逆转认知障碍和神经退行性进展的化合物。 本发明还涉及基于大脑中早老素功能的增强或恢复的阿尔茨海默病治疗的发展。 基于本文所述的发现,本发明进一步涉及开发用于检测人类个体中功能性早老素缺乏症的测定法,优选通过分析早老素底物,其可以提供可用于诊断阿尔茨海默氏病的生物标志物。