Arneson Douglas, Zhang Yong, Yang Xia, Narayanan Manikandan
Department of Integrative Biology and Physiology, University of California Los Angeles, Los Angeles 90095, CA, USA.
J Genet. 2018 Jul;97(3):795-806.
Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis are pressing health concerns in modern societies for which effective therapies are still lacking. Recent high-throughput genomic technologies have enabled genome-scale, multidimensional investigations to facilitate a better understanding of the underlying mechanisms and the identification of novel targets. Here we review the molecular insights gained through such studies, and compare the similarities and differences between neurodegenerative diseases revealed by systems genomics and gene network modelling approaches. We focus specifically on the shared mechanisms at multiple molecular scales ranging from genetic factors to gene expression to network-level features of gene regulation, and whenever possible also point out mechanisms that distinguish one disease from another. Our review sets the stage for similar genomewide inspection in the future on shared/distinct features of neurodegenerative diseases at the levels of cellular, proteomic or epigenomic signatures, and how these features may interact to determine the progression and treatment response of different diseases afflicting the same individual.
诸如阿尔茨海默病、帕金森病和肌萎缩侧索硬化症等神经退行性疾病是现代社会中紧迫的健康问题,目前仍缺乏有效的治疗方法。最近的高通量基因组技术已能够进行全基因组规模的多维研究,以促进对潜在机制的更好理解和新靶点的识别。在此,我们回顾通过此类研究获得的分子见解,并比较系统基因组学和基因网络建模方法所揭示的神经退行性疾病之间的异同。我们特别关注从遗传因素到基因表达再到基因调控的网络层面特征等多个分子尺度上的共同机制,并尽可能指出区分一种疾病与另一种疾病的机制。我们的综述为未来在细胞、蛋白质组或表观基因组特征水平上对神经退行性疾病的共同/独特特征进行类似的全基因组检查奠定了基础,以及这些特征如何相互作用以确定影响同一个体的不同疾病的进展和治疗反应。