Enzymatic degradation of heparan sulfate subdomains that are accumulated in cerebral amyloid plaques

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590349
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Nagoya University
• Principal Investigator: UCHIMURA Kenji 名古屋大学, 医学(系)研究科(研究院), 特任准教授 (20450835)
• Co-Investigator(Kenkyū-buntansha): KADOMATSU Kenji 名古屋大学, 大学院医学研究科, 教授 (80204519)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 糖鎖 / 酵素 / 生体分子 / 脳神経疾患

Outline of Final Research Achievements

Alzheimer's disease (AD) is characterized by cerebral amyloid plaques, which are formed by extracellular accumulation of amyloid beta peptides. Heparan sulfate is an extracellular sugar chain found in amyloid plaques in the brain of transgenic AD mouse models and patients with AD. Heparan sulfate subdomains abundant in amyloid plaques of AD mouse brain sections were substantially degraded by Sulf-2, an extracellular endosulfatase. Ectopic expression of Sulf-2 facilitated amyloid clearance mediated by phagocytotic cells, which were cultured with AD mouse brain sections in an ex vivo phagocytosis assay. These results suggest that AD pathogenesis could be regulated by an enzymatic remodeling of extracellular heparan sulfate in AD brains.

Free Research Field

医化学一般