Analysis of the mechanism of tau pathology focusing on O-glycan using Alzheimer's disease model mice.

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20653
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0702:Biology at cellular to organismal levels, and related fields
• Research Institution: Fukushima Medical University
• Principal Investigator: IIJIMA Junko 福島県立医科大学, 保健科学部, 講師 (10559636)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: tau / Alzheimer's disease / O-glycan

Outline of Final Research Achievements

Since specific antibodies are necessary to analyze the function of O-glycosylation of tau, antibodies were prepared using O-glycosylated tau peptides as antigens. Immunoprecipitation of Wtau-Tg mouse brain was performed using agarose beads to which the antibody was attached, and mass spectral analysis showed that a large amount of mouse IgG was included, and identification of O-glycosylated tau was not achieved. Therefore, we are examining conditions under which antibody IgG does not leak without reducing agents, and conditions in which antibodies are chemically bonded to the bead surface. In addition, brain samples from young and old mice have been prepared, and these will be analyzed in the future.

Free Research Field

医化学

Academic Significance and Societal Importance of the Research Achievements

O型糖鎖はタンパク質のセリンやスレオニンにN-アセチルグルコサミンなどが結合する。その結合部位がリン酸化と同様なため、O型糖鎖はリン酸化の調節に関与すると考えられる。タウでもO型糖鎖修飾によりリン酸化が抑制されること、O-GlcNAc付加酵素を欠損すると神経変性が観察されることが報告された。しかしながらO型糖鎖修飾とリン酸化のスイッチの制御は不明である。タウがリン酸化される時点でADは進行しており、予防・治療のためにはADの早期発見が重要である。ゆえにO型糖鎖に着目した本研究はADの発症機構の新たな知見となり、新規ADマーカーの確立や創薬標的としてADの予防、治療法の開発に貢献すると考える。