2023 Fiscal Year Final Research Report

Elucidation of molecular mechanisms of neuronal differentiation and search for molecular markers of neurodegenerative diseases by glycoproteomics.

Research Project

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Project/Area Number	21H02617
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Review Section	Basic Section 47020:Pharmaceutical analytical chemistry and physicochemistry-related
Research Institution	Yokohama City University
Principal Investigator	Kawasaki Nana 横浜市立大学, 生命医科学研究科, 教授 (20186167)
Co-Investigator(Kenkyū-buntansha)	大橋祥子横浜市立大学, 生命医科学研究科, 特任助手 (00908709) 高倉大輔横浜市立大学, 生命医科学研究科, 特任教員 (90760231)
Project Period (FY)	2021-04-01 – 2024-03-31
Keywords	グライコプロテオミクス / iPS細胞 / 神経分化 / 神経変性疾患 / 糖鎖 / デ―タ非依存的データ取得 / LC/MS/MS / O-GlcNAc
Outline of Final Research Achievements	Glycans are related to various biological phenomena and diseases, but there are limitations in the availability of glycoproteomic approaches and human neural models, and the role of glycans in neuronal differentiation and neurodegenerative diseases has remained unclear. We are investigating the development of glycoproteomic approaches and the use of iPS cell-derived nerves with the aim of searching for glycan diagnostic markers for neurodegenerative diseases. In this study, we developed an O-GlcNAc proteomic approach and combined it with a Parkinson's disease (PD) model and showed that it can be used to explore PD-related OGlcNAc modifications. We also showed that nerve-specific BA2, which was previously found in N-linked glycoproteomics of iPSCs, is involved in neuroaxonal elongation in iPSCs.
Free Research Field	グライコプロテオミクス
Academic Significance and Societal Importance of the Research Achievements	我々が開発しているグライコプロテオミクス手法は、微量の糖鎖修飾を定量解析できる利点がある。また、iPS細胞から作製した疾患モデルは、動物モデルでは解明できないヒト糖鎖の機能解析に適している。グライコプロテオミクス手法と、ヒト神経分化や神経変性疾患モデルを組み合わせた糖鎖研究アプローチは、これまで技術的な限界により明らかにできなかったヒト神経分化や神経変性疾患における糖鎖の役割を明らかにし、糖鎖診断マーカーおよび創薬ターゲットの特定につながるものと期待される。