Department of Cell and Developmental Biology, University College London, Gower Street, London, WC1E 6BT, UK.
Pflugers Arch. 2012 Jul;464(1):111-21. doi: 10.1007/s00424-012-1112-0. Epub 2012 May 22.
Understanding the mechanisms of neuronal dysfunction and death represents a major frontier in contemporary medicine, involving the acute cell death in stroke, and the attrition of the major neurodegenerative diseases, including Parkinson's, Alzheimer's, Huntington's and Motoneuron diseases. A growing body of evidence implicates mitochondrial dysfunction as a key step in the pathogenesis of all these diseases, with the promise that mitochondrial processes represent valuable potential therapeutic targets. Each disease is characterised by the loss of a specific vulnerable population of cells--dopaminergic neurons in Parkinson's disease, spinal motoneurons in Motoneuron disease, for example. We discuss the possible roles of cell type-specific calcium signalling mechanisms in defining the pathological phenotype of each of these major diseases and review central mechanisms of calcium-dependent mitochondrial-mediated cell death.
了解神经元功能障碍和死亡的机制是当代医学的一个主要前沿领域，涉及中风时的急性细胞死亡，以及包括帕金森病、阿尔茨海默病、亨廷顿病和运动神经元病在内的主要神经退行性疾病的衰退。越来越多的证据表明，线粒体功能障碍是所有这些疾病发病机制中的关键步骤，这表明线粒体过程是有价值的潜在治疗靶点。每种疾病的特征都是特定易损细胞群体的丧失——例如帕金森病中的多巴胺能神经元，运动神经元病中的脊髓运动神经元。我们讨论了细胞类型特异性钙信号机制在定义这些主要疾病的病理表型中的可能作用，并回顾了钙依赖性线粒体介导的细胞死亡的中心机制。
