CNR, Institute for Systems Analysis and Computer Science, Via Dei Taurini 19, 00185 Rome, Italy; IRCCS Fondazione Santa Lucia, Via Del Fosso di Fiorano 65, 00143 Rome, Italy.
CNR, Institute for Biomedical Research and Innovation, Via Paolo Gaifami, 18, 95126, Catania, Italy.
Ageing Res Rev. 2020 Sep;62:101121. doi: 10.1016/j.arr.2020.101121. Epub 2020 Jul 9.
A plethora of genetic and molecular mechanisms have been implicated in the pathophysiology of the heterogeneous and multifactorial amyotrophic lateral sclerosis (ALS) disease, and hence the conventional "one target-one drug" paradigm has failed so far to provide effective therapeutic solutions, precisely because of the complex nature of ALS. This review intends to highlight how the integration of emerging "omics" approaches may provide a rational foundation for the comprehensive exploration of molecular pathways and dynamic interactions involved in ALS, for the identification of candidate targets and biomarkers that will assist in the rapid diagnosis and prognosis, lastly for the stratification of patients into different subgroups with the aim of personalized therapeutic strategies. To this purpose, particular emphasis will be placed on some potential therapeutic targets, including neurotrophic factors and histamine signaling that both have emerged as dysregulated at different omics levels in specific subgroups of ALS patients, and have already shown promising results in in vitro and in vivo models of ALS. To conclude, we will discuss about the utility of using integrated omics coupled with network-based approaches to provide additional guidance for personalization of medicine applications in ALS.
大量的遗传和分子机制被牵涉到肌萎缩侧索硬化症（ALS）这种异质性和多因素疾病的病理生理学中，因此传统的“一个靶点一种药物”的模式迄今为止未能提供有效的治疗方法，正是因为 ALS 的复杂性。这篇综述旨在强调新兴的“组学”方法的整合如何为全面探索 ALS 中涉及的分子途径和动态相互作用提供合理的基础，以确定候选靶点和生物标志物，从而有助于快速诊断和预后，最后将患者分层到不同的亚组中，以实现个体化的治疗策略。为此，将特别强调一些潜在的治疗靶点，包括神经营养因子和组胺信号，它们在 ALS 患者的特定亚组中在不同的组学水平上都出现了失调，并在 ALS 的体外和体内模型中已经显示出有前景的结果。最后，我们将讨论使用整合组学和基于网络的方法的实用性，为 ALS 中的个体化医学应用提供额外的指导。
