The Key Laboratory for Biomedical Photonics of MOE at Wuhan National Laboratory for Optoelectronics-Hubei Bioinformatics & Molecular Imaging Key Laboratory, Systems Biology Theme, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China.
Britton Chance Center for Biomedical Photonics, MoE Key Laboratory for Biomedical Photonics, School of Engineering Sciences, Innovation Institute, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan, 430074, China.
Anal Bioanal Chem. 2023 Sep;415(23):5575-5588. doi: 10.1007/s00216-023-04848-8. Epub 2023 Jul 15.
Glycosylation is one of the most common types of post-translational modifications in mammals. It is well known that N-glycans play a key role in cell adhesion, differentiation, synapsis, and myelination during the development of the mammalian central nervous system (CNS). Neuropathological symptoms (such as epilepsy and Alzheimer's disease) are usually accompanied by N-glycosylation changes. In this study, we extracted N-glycan chains from eight regions of the mouse brain, and combined high-throughput, high-resolution matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS) with the Fmoc N-hydroxysuccinimide ester (Fmoc-OSU) derivatization method to improve the sensitivity of glycan detection to characterize the total N-glycans in the mouse brain. A total of 96 N-glycan moieties were detected. An exhaustive examination of the relative abundance of N-glycans, coupled with a comparative analysis of differences, has uncovered discernible variations of statistical significance, including high mannose, fucosylated, sialylated, and galactosylated N-glycans. According to our investigations, a thorough and regionally specific cartography of glycans within the brain can facilitate the investigation of glycan-mediated mechanisms related to both the developmental trajectory and functional output of the brain. Additionally, this approach may serve as a basis for identifying potential biomarkers that are relevant to various brain-associated pathologies.
糖基化是哺乳动物中最常见的翻译后修饰类型之一。众所周知，N-聚糖在哺乳动物中枢神经系统（CNS）的发育过程中在细胞黏附、分化、突触形成和髓鞘形成中起着关键作用。神经病理学症状（如癫痫和阿尔茨海默病）通常伴随着 N-聚糖的变化。在这项研究中，我们从老鼠大脑的 8 个区域提取了 N-聚糖链，并结合了高通量、高分辨率的基质辅助激光解吸/电离飞行时间质谱（MALDI-TOF/MS）和 Fmoc N-羟基琥珀酰亚胺酯（Fmoc-OSU）衍生化方法，以提高糖检测的灵敏度，从而对老鼠大脑中的总 N-聚糖进行特征分析。共检测到 96 种 N-聚糖部分。对 N-聚糖相对丰度的详尽检查，以及差异的比较分析，揭示了可辨别的具有统计学意义的变化，包括高甘露糖、岩藻糖基化、唾液酸化和半乳糖基化 N-聚糖。根据我们的研究，对大脑内糖基的全面和区域特异性绘图可以促进对与大脑发育轨迹和功能输出相关的糖介导机制的研究。此外，这种方法可以作为鉴定与各种与大脑相关的病理相关的潜在生物标志物的基础。
