Sulf2-remodeling of heparan sulfate present in brain amyloids

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K08265
• 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, 招へい教員 (20450835)
• Co-Investigator(Kenkyū-buntansha): 門松 健治 名古屋大学, 医学系研究科, 教授 (80204519)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 糖鎖 / 酵素 / 生体分子 / 脳神経疾患

Outline of Final Research Achievements

Extracellular accumulation of amyloid beta peptides is a character of cerebral amyloid plaques in Alzheimer's disease. Heparan sulfate is an extracellular carbohydrate chain found in amyloid plaques in the brain of transgenic Alzheimer's model mice and patients with Alzheimer's disease. Highly sulfated subdomains within heparan sulfate chains are abundant in amyloid plaques of Alzheimer's mouse brains. Degradation of these subdomains may be a potential approach to activate microglial clearance of the plaques in Alzheimer's brain. We tested if the transgenic expression of an extracellular sulfatase in Alzheimer's model mice could facilitate removal of the subdomains and attenuate cerebral amyloid plaque formation. We have shown that a cell type-specific expression of an extracellular sulfatase resulted in negative regulation of amyloid plaque formation. An enzymatic remodeling of extracellular heparan sulfates in the brain can perhaps control Alzheimer’s pathogenesis.

Free Research Field

糖鎖生物学