IRCCS Mondino Foundation, 27100 Pavia, Italy.
Department of Brain and Behavioral Sciences, University of Pavia, Via Forlanini 6, 27100 Pavia, Italy.
Int J Mol Sci. 2022 Feb 25;23(5):2580. doi: 10.3390/ijms23052580.
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, characterized by the progressive loss of lower motor neurons, weakness and muscle atrophy. ALS lacks an effective cure and diagnosis is often made by exclusion. Thus, it is imperative to search for biomarkers. Biomarkers can help in understanding ALS pathomechanisms, identification of targets for treatment and development of effective therapies. Peripheral blood mononuclear cells (PBMCs) represent a valid source for biomarkers compared to cerebrospinal fluid, as they are simple to collect, and to plasma, because of the possibility of detecting lower expressed proteins. They are a reliable model for patients' stratification. This review provides an overview on PBMCs as a potential source of biomarkers in ALS. We focused on altered RNA metabolism (coding/non-coding RNA), including RNA processing, mRNA stabilization, transport and translation regulation. We addressed protein abnormalities (aggregation, misfolding and modifications); specifically, we highlighted that SOD1 appears to be the most characterizing protein in ALS. Finally, we emphasized the correlation between biological parameters and disease phenotypes, as regards prognosis, severity and clinical features. In conclusion, even though further studies are needed to standardize the use of PBMCs as a tool for biomarker investigation, they represent a promising approach in ALS research.
肌萎缩侧索硬化症（ALS）是一种毁灭性的神经退行性疾病，其特征是下运动神经元逐渐丧失、肌肉无力和萎缩。ALS 缺乏有效的治疗方法，通常通过排除法进行诊断。因此，寻找生物标志物至关重要。生物标志物可以帮助我们理解 ALS 的发病机制、确定治疗靶点并开发有效的治疗方法。与脑脊液相比，外周血单核细胞（PBMCs）作为生物标志物的来源更为可靠，因为其易于采集，而且与血浆相比，更有可能检测到低表达蛋白。它们是患者分层的可靠模型。本综述概述了 PBMCs 作为 ALS 生物标志物的潜在来源。我们重点介绍了改变的 RNA 代谢（编码/非编码 RNA），包括 RNA 加工、mRNA 稳定性、运输和翻译调控。我们还讨论了蛋白质异常（聚集、错误折叠和修饰）；具体而言，我们强调了 SOD1 似乎是 ALS 中最具特征性的蛋白质。最后，我们强调了生物学参数与疾病表型之间的相关性，包括预后、严重程度和临床特征。总之，尽管需要进一步的研究来标准化 PBMCs 作为生物标志物研究工具的使用，但它们是 ALS 研究中很有前途的方法。
