Jaskova Katarina, Pavlovicova Michaela, Jurkovicova Dana
Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences, Vlarska 5, 833 34 Bratislava, Slovak Republic.
Gen Physiol Biophys. 2012 Dec;31(4):375-82. doi: 10.4149/gpb_2012_053.
Neurodegeneration comprises assembly of pathophysiological events that gives rise to a progressive loss of neuronal structure and function including cellular damage, diseases development or cellular death. Neurons respond by adjusting signaling pathways, from gene expression to morphological changes. In most of these processes, Ca2+ signaling plays a pivotal role. By increasing the Ca2+ concentration, the cell responds to neuronal, neurotrophic and other growth factor stimuli, however, the molecular mechanism of Ca2+-dependent neurite outgrowth and development yet requires further elucidation. Here we focus on the role of Ca2+ and selected Ca2+ transporters involved in processes of CNS neurodegeneration - inositol 1,4,5-trisphosphate (IP3Rs) and ryanodine receptors (RyRs), considering the fact that these receptors may be important "sensors" of disturbed intracellular calcium homeostasis. We propose that in vitro cellular models could serve as suitable experimental systems for the determination of the role that these receptors play in neuropathological conditions. Recognition of the principles, key players and regulatory processes may elucidate the role of Ca2+ in the regulation of neuronal proliferation, development and differentiation, growth and axon navigation in neurodegenerative and regenerative processes. This may provide a new insight and also discovery of novel therapeutic-targeting possibilities for severe neurological disorders and pathophysiological changes.
神经退行性变包括一系列病理生理事件，这些事件导致神经元结构和功能的渐进性丧失，包括细胞损伤、疾病发展或细胞死亡。神经元通过调整信号通路做出反应，从基因表达到形态变化。在大多数这些过程中，Ca2+信号传导起着关键作用。通过增加Ca2+浓度，细胞对神经元、神经营养因子和其他生长因子刺激做出反应，然而，Ca2+依赖性神经突生长和发育的分子机制仍需进一步阐明。在这里，我们关注Ca2+以及参与中枢神经系统神经退行性变过程的特定Ca2+转运体——肌醇1,4,5-三磷酸受体（IP3Rs）和兰尼碱受体（RyRs）的作用，考虑到这些受体可能是细胞内钙稳态紊乱的重要“传感器”。我们提出，体外细胞模型可作为合适的实验系统，用于确定这些受体在神经病理条件下所起的作用。认识这些原理、关键参与者和调节过程可能会阐明Ca2+在神经退行性变和再生过程中对神经元增殖、发育和分化、生长以及轴突导航的调节作用。这可能为严重神经系统疾病和病理生理变化提供新的见解，并发现新的治疗靶点可能性。
