多发性硬化症(MS)是中枢神经系统(CNS)的炎性脱髓鞘和退行性疾病。虽然炎症反应得到有效治疗,进展疗法是稀缺和次优的,和生物标志物来预测疾病的进程是不够的。MS的治疗或预防措施需要了解组织损伤部位的核心病理事件。系统生物学的新颖性已经出现,并为对中枢神经系统内关键病理途径的更细粒度理解铺平了道路。但是他们也提出了仍然没有答案的问题。这里,我们系统地回顾了组织和单细胞/细胞核CNS组学的功效,并讨论了整合到临床实践中的主要差距.从1997年到2021年10月,系统搜索确定了49个中枢神经系统转录组和11个蛋白质组研究。开创性的分子发现表明,MS影响整个大脑和所有常驻细胞类型。尽管结果不一致,研究表明信号素的转录物/蛋白质增加,热休克蛋白,髓鞘蛋白,载脂蛋白和HLA。不同的病变以不同的星形胶质细胞和小胶质细胞极化为特征,少突形成改变,和特定神经元亚型的变化。在所有白质病变类型中,CXCL12、SCD、CD163高表达,和STAT6-和TGFβ-信号增加。在灰质病变中,肿瘤坏死因子信号似乎驱动细胞死亡,尤其是表达CUX2的神经元可能对神经变性敏感。细胞和病变水平的巨大异质性可能是MS临床异质性的基础,在临床实践中,它可能比目前的疾病表型更为复杂。系统生物学尚未解开MS之谜,但它发现了多种分子和网络可能有助于发病机制。然而,这些结果大多是描述性的;分子变化的重点功能研究可能会为更好的解释开辟道路。可接受质量准则或对低质量数据结果的认识,标准化的计算和生物管道可能有助于克服有限的组织可用性和组学的“快照”问题。这些可能有助于识别核心病理事件,并指出临床预防重点的方向。
Multiple sclerosis (MS) is an inflammatory demyelinating and degenerative disease of the central nervous system (CNS). Although inflammatory responses are efficiently treated, therapies for progression are scarce and suboptimal, and biomarkers to predict the disease course are insufficient. Cure or preventive measures for MS require knowledge of core pathological events at the site of the tissue damage. Novelties in systems biology have emerged and paved the way for a more fine-grained understanding of key pathological pathways within the CNS, but they have also raised questions still without answers. Here, we systemically
review the power of tissue and single-cell/nucleus CNS omics and discuss major gaps of integration into the clinical practice. Systemic search identified 49 transcriptome and 11 proteome studies of the CNS from 1997 till October 2021. Pioneering molecular discoveries indicate that MS affects the whole brain and all resident cell types. Despite inconsistency of results, studies imply increase in transcripts/proteins of semaphorins, heat shock proteins, myelin proteins, apolipoproteins and HLAs. Different lesions are characterized by distinct astrocytic and microglial polarization, altered oligodendrogenesis, and changes in specific neuronal subtypes. In all white matter lesion types, CXCL12, SCD, CD163 are highly expressed, and STAT6- and TGFβ-signaling are increased. In the grey matter lesions, TNF-signaling seems to drive cell death, and especially CUX2-expressing neurons may be susceptible to neurodegeneration. The vast heterogeneity at both cellular and lesional levels may underlie the clinical heterogeneity of MS, and it may be more complex than the current disease phenotyping in the clinical practice. Systems biology has not solved the mystery of MS, but it has discovered multiple molecules and networks potentially contributing to the pathogenesis. However, these results are mostly descriptive; focused functional studies of the molecular changes may open up for a better interpretation. Guidelines for acceptable quality or awareness of results from low quality data, and standardized computational and biological pipelines may help to overcome limited tissue availability and the \"snap shot\" problem of omics. These may help in identifying core pathological events and point in directions for focus in clinical prevention.