The inhibition of gamma-secretase as a therapeutic approach to Alzheimer's disease.
The inhibition of gamma-secretase as a therapeutic approach to Alzheimer's disease.
复制标题
抑制γ-分泌酶作为阿尔茨海默病的治疗方法。
作者：
T. Tomita;T. Iwatsubo
阿尔茨海默病是一种致残性神经退行性疾病，目前尚无有效治疗方法。遗传和生物学研究提供证据表明，淀粉样β肽（Abeta）的产生和沉积是阿尔茨海默病的病因。γ-分泌酶是生成Abeta C末端的关键酶，决定了其聚集性和沉积速度。通过抑制γ-分泌酶活性来调节Abeta产生的药物可以为阿尔茨海默病提供有效的治疗，尽管最近的研究表明γ-分泌酶在细胞信号传导中发挥着重要作用。本综述重点关注研究γ-分泌酶生物学的研究，并为开发有效且选择性的γ-分泌酶抑制剂作为治疗阿尔茨海默病的药物提供了方向。
Alzheimer's disease is a dementing neurodegenerative disorder for which there is no effective treatment at present. Genetic and biological studies provide evidence that the production and deposition of amyloid-beta peptides (Abeta contribute to the etiology of Alzheimer's disease. gamma-Secretase is the pivotal enzyme in generating the C terminus of Abeta which determines its aggregability and speed of deposition. Drugs that regulate the production of Abeta by inhibiting gamma-secretase activity could provide an effective therapy for Alzheimer's disease, although recent studies suggest that gamma-secretase plays important roles in cellular signaling. This review focuses on studies of the gamma-secretase biology and provides the direction for developing effective and selective gamma-secretase inhibitors as drugs for the treatment of Alzheimer's disease.