Involvement of abnormal glycosylation in the pathogenesis of Parkinson's disease

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H03584
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: Department of Clinical Research, National Hospital Organization Tokushima National Hospital
• Principal Investigator: Kurota Yukiko 独立行政法人国立病院機構徳島病院(臨床研究部), その他部局等, 研究員(移行) (70398014)
• Co-Investigator(Kenkyū-buntansha): 三ツ井 貴夫 独立行政法人国立病院機構徳島病院(臨床研究部), その他部局等, その他 (80294726)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: パーキンソン病

Outline of Final Research Achievements

We have found that Parkin is intracellularly modified with O-GlcNAc (O-GlcNAcylation) and localized to mitochondria. When the deglycosylating enzymes O-glycosidase and Sialidase A were added simultaneously to the glycosylated parkin, there was a shift in the height of the bands of the non-glycosylated Parkin. Monosaccharide analysis suggested that Parkin was O-glycosylated.Glycoblotting analysis showed that (HexNAc)1 was the major component, and the Click-iT reaction also confirmed O-GlcNAc modification.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

本研究で得られた知見より、哺乳動物細胞内でパーキンの一部はO-GlcNAcを含むO型糖鎖が付加されていることは確実である。我々は本研究においてO-GlcNAc 修飾機構の異常がパーキンソン病の発症要因になりうるか否かを、家族性パーキンソン病である PARK2 において、さらには孤発性パーキンソン病において明らかにするために計画された。