Faculty of Science and Engineering, Department of Molecular Pharmacology, Groningen Research Institute of Pharmacy (GRIP), University of Groningen, 9713 AV Groningen, the Netherlands; Medical School, Neurology Department, University of São Paulo (USP), 01246903 São Paulo, Brazil.
Faculty of Science and Engineering, Department of Molecular Pharmacology, Groningen Research Institute of Pharmacy (GRIP), University of Groningen, 9713 AV Groningen, the Netherlands.
Int J Biochem Cell Biol. 2020 Jun;123:105748. doi: 10.1016/j.biocel.2020.105748. Epub 2020 Apr 27.
Population aging, as well as the handling of age-associated diseases, is a worldwide increasing concern. Among them, Alzheimer's disease stands out as the major cause of dementia culminating in full dependence on other people for basic functions. However, despite numerous efforts, in the last decades, there was no new approved therapeutic drug for the treatment of the disease. Calcium-activated potassium channels have emerged as a potential tool for neuronal protection by modulating intracellular calcium signaling. Their subcellular localization is determinant of their functional effects. When located on the plasma membrane of neuronal cells, they can modulate synaptic function, while their activation at the inner mitochondrial membrane has a neuroprotective potential via the attenuation of mitochondrial reactive oxygen species in conditions of oxidative stress. Here we review the dual role of these channels in the aging phenotype and Alzheimer's disease pathology and discuss their potential use as a therapeutic tool.
人口老龄化以及与年龄相关疾病的处理是全球日益关注的问题。其中,阿尔茨海默病是导致痴呆症的主要原因,最终导致患者完全依赖他人来完成基本功能。然而,尽管过去几十年进行了大量研究,但仍没有新的批准用于治疗该疾病的治疗性药物。钙激活钾通道已成为通过调节细胞内钙信号来保护神经元的潜在工具。其亚细胞定位决定了其功能效应。当位于神经元细胞的质膜上时,它们可以调节突触功能,而当其在内线粒体膜上激活时,通过在氧化应激条件下减弱线粒体活性氧,可以发挥神经保护作用。在这里,我们回顾了这些通道在衰老表型和阿尔茨海默病病理中的双重作用,并讨论了它们作为治疗工具的潜在用途。