Neurological aspects of human glycosylation disorders.
Neurological aspects of human glycosylation disorders.
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DOI：
10.1146/annurev-neuro-071714-034019
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发表时间：
2015-07-08
影响因子：
13.9
通讯作者：
Patterson MC
中科院分区：
文献类型：
--
作者：
Freeze HH;Eklund EA;Ng BG;Patterson MC
这篇综述将介绍糖基化的原理，描述相关的糖基化途径及其相关疾病，并强调一些继续挑战研究人员的神经学方面和问题。目前已知有 100 多种罕见的人类遗传性疾病是由不同糖基化途径缺陷引起的。大多数这些疾病影响中枢和/或周围神经系统。患者通常患有发育迟缓/智力障碍、肌张力低下、癫痫发作、神经病变和多器官系统代谢异常。这些疾病之间存在很大的临床多样性，因为所有细胞类型对蛋白质和脂质的糖基化程度不同。患者体内有数百种错误糖基化产物，影响细胞信号传导、细胞间相互作用和细胞迁移等无数过程。聚糖组成和功能的巨大复杂性以及有限的分析工具阻碍了导致病理的关键糖基化分子的识别，并且迄今为止很少有关键靶蛋白被精确定位。
This review will present principles of glycosylation, describe the relevant glycosylation pathways and their related disorders, and highlight some of the neurological aspects and issues that continue to challenge researchers. Over 100 rare human genetic disorders that result from deficiencies in the different glycosylation pathways are known today. Most of these disorders impact the central and/or peripheral nervous systems. Patients typically have developmental delay/intellectual disability, hypotonia, seizures, neuropathy, and metabolic abnormalities in multiple organ systems. Between these disorders there is great clinical diversity because all cell types differentially glycosylate proteins and lipids. The patients have hundreds of mis-glycosylated products afflicting a myriad of processes including cell signaling, cell-cell interaction and cell migration. This vast complexity in glycan composition and function, along with limited analytic tools has impeded the identification of key glycosylated molecules that cause pathologies, and to date few critical target proteins have been pinpointed.