High content analysis in amyotrophic lateral sclerosis.
High content analysis in amyotrophic lateral sclerosis.
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DOI：
10.1016/j.mcn.2016.12.001
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发表时间：
2017-04
期刊：
影响因子：
--
通讯作者：
Kaspar BK
中科院分区：
文献类型：
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作者：
Rinaldi F;Motti D;Ferraiuolo L;Kaspar BK
肌萎缩侧索硬化症（ALS）是一种以运动神经元进行性丧失为特征的破坏性疾病。神经元、星形胶质细胞、少突胶质细胞和小胶质细胞都在ALS的发病和进展中经历病理改变。已经确定了许多参与该疾病发病机制的基因，但尚未确定对ALS分子机制的完整理解。目前，受ALS影响的人从诊断开始的预期寿命只有两到五年。对治疗方法的研究进展缓慢，而且大多不成功，这使得患者迫切需要更好的治疗方法。直到最近，大多数临床前研究利用可用的ALS动物模型。在过去的几年中，用于分离患者细胞并分化为相关细胞类型的新方案的开发为ALS建模提供了新的工具，这些工具可能与疾病本身更相关，因为它们直接来自患者。干细胞的使用显示出通过扩大我们对该疾病的理解来促进ALS研究的希望，并有助于确定潜在的新治疗靶点和治疗方法来帮助患者。通过将自动图像采集沿着与数字图像分析相结合，高含量分析（HCA）的进步有能力推动ALS研究向前发展。使用现代HCA机器，可以在短短几个小时内，在数百种（如果不是数千种）药物和化合物的刺激下观察细胞形态和存活的变化。在这篇文章中，我们将总结ALS的主要分子和细胞标志，描述在过去几年中开发的体外模型所提供的进展，并回顾HCA应用于ALS领域的研究。
Amyotrophic Lateral Sclerosis (ALS) is a devastating disease characterized by the progressive loss of motor neurons. Neurons, astrocytes, oligodendrocytes and microglial cells all undergo pathological modifications in the onset and progression of ALS. A number of genes involved in the etiopathology of the disease have been identified, but a complete understanding of the molecular mechanisms of ALS has yet to be determined. Currently, people affected by ALS have a life expectancy of only two to five years from diagnosis. The search for a treatment has been slow and mostly unsuccessful, leaving patients in desperate need of better therapies. Until recently, most pre-clinical studies utilized the available ALS animal models. In the past years, the development of new protocols for isolation of patient cells and differentiation into relevant cell types has provided new tools to model ALS, potentially more relevant to the disease itself as they directly come from patients. The use of stem cells is showing promise to facilitate ALS research by expanding our understanding of the disease and help to identify potential new therapeutic targets and therapies to help patients. Advancements in High Content Analysis (HCA) have the power to contribute to move ALS research forward by combining automated image acquisition along with digital image analysis. With modern HCA machines it is possible, in a period of just a few hours, to observe changes in morphology and survival of cells, under the stimulation of hundreds, if not thousands of drugs and compounds. In this article, we will summarize the major molecular and cellular hallmarks of ALS, describe the advancements provided by the in vitro models developed in the last few years, and review the studies that have applied HCA to the ALS field to date.