钙调神经磷酸酶在错误折叠蛋白和内质网应激引起的神经变性中的作用。
Role of calcineurin in neurodegeneration produced by misfolded proteins and endoplasmic reticulum stress.
机构信息
Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, The University of Texas Medical School at Houston, 6431 Fannin St., Houston, TX, United States.
出版信息
Curr Opin Cell Biol. 2011 Apr;23(2):223-30. doi: 10.1016/j.ceb.2010.12.006. Epub 2011 Feb 2.
Abstract
A hallmark event in neurodegenerative diseases is the accumulation of misfolded aggregated proteins in the brain leading to neuronal dysfunction and disease. Compelling evidence suggests that misfolded proteins damage cells by inducing endoplasmic reticulum (ER) stress and alterations in calcium homeostasis. Changes in cytoplasmic calcium concentration lead to unbalances on several signaling pathways. Recent data suggest that calcium-mediated hyperactivation of calcineurin (CaN), a key phosphatase in the brain, triggers synaptic dysfunction and neuronal death, the two central events responsible for brain degeneration in neurodegenerative diseases. Therefore, blocking CaN hyper-activation might be a promising therapeutic strategy to prevent brain damage in neurodegenerative diseases.
摘要
神经退行性疾病的一个标志事件是错误折叠的聚集蛋白在大脑中的积累，导致神经元功能障碍和疾病。有强有力的证据表明，错误折叠的蛋白质通过诱导内质网（ER）应激和钙稳态的改变来损伤细胞。细胞质钙离子浓度的变化导致几个信号通路的失衡。最近的数据表明，钙介导的脑中关键磷酸酶钙调神经磷酸酶（CaN）的过度激活触发了突触功能障碍和神经元死亡，这是导致神经退行性疾病中大脑退化的两个中心事件。因此，阻断 CaN 的过度激活可能是预防神经退行性疾病中脑损伤的一种有前途的治疗策略。
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