Calvo-Rodriguez Maria, Bacskai Brian J
Alzheimer Research Unit, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, 114 16th Street, Charlestown, MA 02129, USA.
Alzheimer Research Unit, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, 114 16th Street, Charlestown, MA 02129, USA.
Trends Neurosci. 2021 Feb;44(2):136-151. doi: 10.1016/j.tins.2020.10.004. Epub 2020 Nov 4.
Mitochondrial dysfunction has been implicated in the pathogenesis of almost all neurological diseases, including Alzheimer's disease (AD). Historically, a primary focus in this context has been the link between mitochondrial dynamics and amyloid β toxicity. Recent evidence suggests that dysregulation of mitochondrial calcium homeostasis is also related to tau and other risk factors in AD, although an ongoing challenge in the field is that data collected from different models or experimental settings have not always been consistent. We examine recent literature on mitochondrial dysregulation in AD, with special emphasis on mitochondrial calcium. We include data from in vitro systems, genetic animal models, and AD-derived human tissue, and discuss whether mitochondrial calcium transporters should be proposed as therapeutic candidates for the development of neuroprotective drugs against AD.
线粒体功能障碍几乎与所有神经疾病的发病机制都有关联，包括阿尔茨海默病（AD）。从历史上看，这方面的主要关注点一直是线粒体动力学与淀粉样β毒性之间的联系。最近的证据表明，线粒体钙稳态失调也与AD中的tau蛋白及其他风险因素有关，尽管该领域目前面临的一个挑战是，从不同模型或实验环境中收集的数据并不总是一致的。我们研究了近期关于AD中线粒体失调的文献，特别关注线粒体钙。我们纳入了来自体外系统、基因动物模型和AD患者来源的人体组织的数据，并讨论了线粒体钙转运体是否应被视为开发抗AD神经保护药物的治疗候选靶点。
