Liang Jingyi, Kulasiri Don, Samarasinghe Sandhya
Centre for Advanced Computational Solutions (C-fACS), Lincoln University, Christchurch, New Zealand; Department of Molecular Biosciences, Lincoln University, Christchurch, New Zealand.
Centre for Advanced Computational Solutions (C-fACS), Lincoln University, Christchurch, New Zealand; Department of Molecular Biosciences, Lincoln University, Christchurch, New Zealand.
Biosystems. 2015 Aug;134:1-15. doi: 10.1016/j.biosystems.2015.05.003. Epub 2015 May 19.
Alzheimer's disease (AD) is a devastating, incurable neurodegenerative disease affecting millions of people worldwide. Dysregulation of intracellular Ca(2+) signaling has been observed as an early event prior to the presence of clinical symptoms of AD and is believed to be a crucial factor contributing to its pathogenesis. The progressive and sustaining increase in the resting level of cytosolic Ca(2+) will affect downstream activities and neural functions. This review focuses on the issues relating to the increasing Ca(2+) release from the endoplasmic reticulum (ER) observed in AD neurons. Numerous research papers have suggested that the dysregulation of ER Ca(2+) homeostasis is associated with mutations in the presenilin genes and amyloid-β oligomers. These disturbances could happen at many different points in the signaling process, directly affecting ER Ca(2+) channels or interfering with related pathways, which makes it harder to reveal the underlying mechanisms. This review paper also shows that computational modeling is a powerful tool in Ca(2+) signaling studies and discusses the progress in modeling related to Ca(2+) dysregulation in AD research.
阿尔茨海默病（AD）是一种毁灭性的、无法治愈的神经退行性疾病，影响着全球数百万人。细胞内Ca(2+)信号失调已被观察到是AD临床症状出现之前的早期事件，并且被认为是其发病机制的关键因素。胞质Ca(2+)静息水平的渐进性和持续性升高会影响下游活动和神经功能。本综述聚焦于与AD神经元中内质网（ER）Ca(2+)释放增加相关的问题。众多研究论文表明，ER Ca(2+)稳态失调与早老素基因突变和淀粉样β寡聚体有关。这些干扰可能发生在信号传导过程的许多不同点，直接影响ER Ca(2+)通道或干扰相关途径，这使得揭示潜在机制变得更加困难。本文还表明，计算建模是Ca(2+)信号研究中的有力工具，并讨论了AD研究中与Ca(2+)失调相关的建模进展。
