Yuan J, Yankner B A
Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Nature. 2000 Oct 12;407(6805):802-9. doi: 10.1038/35037739.
Neuronal apoptosis sculpts the developing brain and has a potentially important role in neurodegenerative diseases. The principal molecular components of the apoptosis programme in neurons include Apaf-1 (apoptotic protease-activating factor 1) and proteins of the Bcl-2 and caspase families. Neurotrophins regulate neuronal apoptosis through the action of critical protein kinase cascades, such as the phosphoinositide 3-kinase/Akt and mitogen-activated protein kinase pathways. Similar cell-death-signalling pathways might be activated in neurodegenerative diseases by abnormal protein structures, such as amyloid fibrils in Alzheimer's disease. Elucidation of the cell death machinery in neurons promises to provide multiple points of therapeutic intervention in neurodegenerative diseases.
神经元凋亡塑造发育中的大脑，并在神经退行性疾病中可能发挥重要作用。神经元凋亡程序的主要分子成分包括凋亡蛋白酶激活因子1（Apaf-1）以及Bcl-2和半胱天冬酶家族的蛋白质。神经营养因子通过关键蛋白激酶级联反应，如磷酸肌醇3激酶/Akt和丝裂原活化蛋白激酶途径，来调节神经元凋亡。在神经退行性疾病中，类似的细胞死亡信号通路可能会被异常蛋白质结构激活，比如阿尔茨海默病中的淀粉样纤维。阐明神经元中的细胞死亡机制有望为神经退行性疾病提供多个治疗干预点。
