Garden Gwenn A, Campbell Brian M
Department of Neurology, University of Washington, Seattle, Washington.
Neuroinflammation DBU, Lundbeck Research USA, Paramus, New Jersey.
Glia. 2016 Oct;64(10):1755-71. doi: 10.1002/glia.22998. Epub 2016 May 26.
There is a growing understanding that aberrant GLIA function is an underlying factor in psychiatric and neurological disorders. As drug discovery efforts begin to focus on glia-related targets, a key gap in knowledge includes the availability of validated biomarkers to help determine which patients suffer from dysfunction of glial cells or who may best respond by targeting glia-related drug mechanisms. Biomarkers are biological variables with a significant relationship to parameters of disease states and can be used as surrogate markers of disease pathology, progression, and/or responses to drug treatment. For example, imaging studies of the CNS enable localization and characterization of anatomical lesions without the need to isolate tissue for biopsy. Many biomarkers of disease pathology in the CNS involve assays of glial cell function and/or response to injury. Each major glia subtype (oligodendroglia, astroglia and microglia) are connected to a number of important and useful biomarkers. Here, we describe current and emerging glial based biomarker approaches for acute CNS injury and the major categories of chronic nervous system dysfunction including neurodegenerative, neuropsychiatric, neoplastic, and autoimmune disorders of the CNS. These descriptions are highlighted in the context of how biomarkers are employed to better understand the role of glia in human CNS disease and in the development of novel therapeutic treatments. GLIA 2016;64:1755-1771.
人们越来越认识到,胶质细胞功能异常是精神和神经疾病的一个潜在因素。随着药物研发工作开始聚焦于与胶质细胞相关的靶点,知识上的一个关键空白在于缺乏经过验证的生物标志物,以帮助确定哪些患者存在胶质细胞功能障碍,或者哪些患者可能通过针对与胶质细胞相关的药物机制而获得最佳疗效。生物标志物是与疾病状态参数具有显著关系的生物学变量,可作为疾病病理、进展和/或药物治疗反应的替代标志物。例如,中枢神经系统的影像学研究能够对解剖学病变进行定位和特征描述,而无需分离组织进行活检。中枢神经系统中许多疾病病理的生物标志物都涉及胶质细胞功能测定和/或对损伤的反应。每一种主要的胶质细胞亚型(少突胶质细胞、星形胶质细胞和小胶质细胞)都与许多重要且有用的生物标志物相关。在此,我们描述了用于急性中枢神经系统损伤以及包括中枢神经系统神经退行性、神经精神性、肿瘤性和自身免疫性疾病在内的慢性神经系统功能障碍主要类别的基于胶质细胞的现有和新兴生物标志物方法。这些描述将在如何利用生物标志物更好地理解胶质细胞在人类中枢神经系统疾病中的作用以及新型治疗方法开发的背景下进行重点阐述。《胶质细胞》2016年;64卷:1755 - 1771页