Division of Pharmacology, Department of Neuroscience, Reproductive and Odontostomatological Sciences, School of Medicine, "Federico II" University of Naples, Via S.Pansini 5, 80131 Napoli, Italy.
Cells. 2019 Oct 8;8(10):1216. doi: 10.3390/cells8101216.
Recent findings in the understanding of amyotrophic lateral sclerosis (ALS) revealed that alteration in calcium (Ca) homeostasis may largely contribute to motor neuron demise. A large part of these alterations is due to dysfunctional Ca-storing organelles, including the endoplasmic reticulum (ER) and mitochondria. Very recently, lysosomal Ca dysfunction has emerged as an important pathological change leading to neuronal loss in ALS. Remarkably, the Ca-storing organelles are interacting with each other at specialized domains controlling mitochondrial dynamics, ER/lysosomal function, and autophagy. This occurs as a result of interaction between specific ionic channels and Ca-dependent proteins located in each structure. Therefore, the dysregulation of these ionic mechanisms could be considered as a key element in the neurodegenerative process. This review will focus on the possible role of lysosomal Ca dysfunction in the pathogenesis of several neurodegenerative diseases, including ALS and shed light on the possibility that specific lysosomal Ca channels might represent new promising targets for preventing or at least delaying neurodegeneration in ALS.
最近在理解肌萎缩侧索硬化症（ALS）方面的发现表明，钙（Ca）稳态的改变可能在很大程度上导致运动神经元死亡。这些改变的很大一部分是由于包括内质网（ER）和线粒体在内的功能失调的 Ca 储存细胞器。最近，溶酶体 Ca 功能障碍已成为导致 ALS 神经元丧失的重要病变。值得注意的是，Ca 储存细胞器在专门的控制线粒体动力学、ER/溶酶体功能和自噬的区域相互作用。这是由于位于每个结构中的特定离子通道和 Ca 依赖性蛋白之间的相互作用而发生的。因此，这些离子机制的失调可能被认为是神经退行性过程中的关键因素。这篇综述将重点讨论溶酶体 Ca 功能障碍在几种神经退行性疾病（包括 ALS）发病机制中的可能作用，并阐明特定的溶酶体 Ca 通道可能代表预防或至少延迟 ALS 神经退行性变的新的有希望的靶点的可能性。
Zotero 插件