Institute of Veterinary Physiology, University of Zurich, Zurich, Switzerland.
Laboratory of Neurodegeneration, International Institute of Molecular and Cell Biology, Warsaw, Poland.
Cell Calcium. 2020 Jul;89:102216. doi: 10.1016/j.ceca.2020.102216. Epub 2020 May 16.
Parkinson's disease (PD) is a major health problem worldwide affecting millions of people and is a result of neurodegeneration in a small part of the brain known as substantia nigra pars compacta. Aberration in mitochondrial Ca homeostasis plays, among several other factors, an important role for the neuronal loss in PD. Mitochondria are vital for cellular physiology, e.g. for ATP generation, and mitochondrial Ca is a key player in cell functioning and survival. Mitochondrial Ca homeostasis is maintained by a fine balance between the activities of proteins mediating the influx and efflux of Ca across mitochondrial membranes. Malfunctioning of these proteins leading to Ca overload promotes ROS generation, which induces cell death by triggering the opening of mitochondrial permeability transition pore. Till now PD remains incurable and the "gold standard" drug which can only delays the disease progression is l-Dopa from the 1960s and therefore, the situation warrants the search for novel targets for the treatment of the PD patients. In this review, we summarize the current views that suggest mitochondrial Ca regulatory pathways are good candidates for the treatment of PD.
帕金森病（PD）是全球范围内的一个主要健康问题，影响着数百万人，是大脑中一小部分称为黑质致密部的神经退行性变的结果。线粒体 Ca 稳态的异常除了其他几个因素外，对于 PD 中的神经元丧失起着重要作用。线粒体对于细胞生理学至关重要，例如生成 ATP，线粒体 Ca 是细胞功能和存活的关键因素。线粒体 Ca 稳态通过调节线粒体膜内外 Ca 流入和流出的蛋白质的活性之间的精细平衡来维持。这些蛋白质的功能障碍导致 Ca 过载，通过触发线粒体通透性转换孔的开放来诱导细胞死亡，从而产生 ROS。到目前为止，PD 仍然无法治愈，20 世纪 60 年代以来唯一可以延缓疾病进展的“金标准”药物是左旋多巴，因此，情况需要寻找治疗 PD 患者的新靶点。在这篇综述中，我们总结了目前的观点，即线粒体 Ca 调节途径是治疗 PD 的候选途径。
