Pediatric Neurology Unit, Dept. of Pediatrics, University of Catania, Via S. Sofia 78, 95125 Catania, Italy.
J Proteomics. 2012 Sep 18;75(17):5123-39. doi: 10.1016/j.jprot.2012.07.007. Epub 2012 Jul 16.
Glycosylation consists in the covalent linkage of a carbohydrate structure to membrane bound and secreted glycoconjugates. It is a common post-translational modification that serves multiple functions in cell differentiation, signaling and intercellular communication. Unlike DNA/RNA/protein, the addition of complex carbohydrates is not-template driven and it is conceivable that both genetics and environmental factors might interact to influence glycosylation machinery in several pathological processes. Over the last few decades, the recognition of Congenital Disorders of Glycosylation (CDG) as an increasing number of genetic diseases of glycosylation with almost constant nervous system involvement, dramatically illustrated the consequences of abnormal glycosylation as improper CNS development and function. In addition, CDG recognition contributed to postulate that aberrant glycosylation processes might play a role in multifactorial, complex CNS diseases. On this context, CNS glycomics explores the effects of possible aberrant glycosylation to identify potential glyco-biomarkers useful for the diagnosis and ultimately for potential intervention strategies in neurological diseases. Up to date, CNS glycomics is an emerging, still uncharted area because of the specificity of CNS glycosylation, the complexity of the neurological disorders and for the inaccessibility and invasiveness of disease relevant samples. Here we review current knowledge on clinical glycomics of nervous system diseases, starting with CDG to include those pediatric and adulthood neuropsychiatric diseases where some evidences suggest that multifactor determinants converge to dysregulate glycosylation. Conventional and mass spectrometry-based high throughput technology for glyco-biomarker detection in CNS diseases is reported.
糖基化是指碳水化合物结构与膜结合和分泌型糖缀合物的共价连接。它是一种常见的翻译后修饰,在细胞分化、信号转导和细胞间通讯中具有多种功能。与 DNA/RNA/蛋白质不同,复杂碳水化合物的添加不是模板驱动的,可以想象遗传和环境因素可能相互作用,影响几种病理过程中的糖基化机制。在过去的几十年中,先天性糖基化紊乱 (CDG) 的认识作为越来越多的糖基化遗传疾病,几乎都涉及神经系统,极大地说明了异常糖基化对中枢神经系统发育和功能的不当影响。此外,CDG 的认识促使人们假设异常糖基化过程可能在多因素、复杂的中枢神经系统疾病中发挥作用。在此背景下,中枢神经系统糖组学探索了可能异常糖基化的影响,以确定潜在的糖基生物标志物,用于神经疾病的诊断,并最终用于潜在的干预策略。迄今为止,中枢神经系统糖组学是一个新兴的、尚未探索的领域,这是由于中枢神经系统糖基化的特异性、神经疾病的复杂性以及疾病相关样本的不可及性和侵入性。本文综述了神经系统疾病临床糖组学的最新知识,从 CDG 开始,包括那些儿科和成年神经精神疾病,其中一些证据表明,多因素决定因素会聚以调节糖基化。报告了中枢神经系统疾病中基于常规和质谱的高通量技术用于糖基生物标志物的检测。