inhibitors of amyloid beta oligomerization in human cerebrospinal fluid

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K19506
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurology
• Research Institution: Kanazawa University
• Principal Investigator: Ikeda Tokuhei 金沢大学, 医学系, 協力研究員 (30755773)
• Research Collaborator: YAMADA Masahito 金沢大学, 医学系, 教授 ; ONO Kenjiro 昭和大学, 医学部, 教授
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: Alzheimer病 / アミロイドβ / オリゴマー

Outline of Final Research Achievements

The purpose of this research was to identify inhibitors of amyloid β (Aβ) oligomerization in human cerebrospinal fluid (CSF). CSF was fractionated using centrifugation through a column and size-exclusion high-performance liquid chromatography. Two CSF fractions had inhibitory effects on Aβ oligomerization, as determined using tandem mass spectrometry. We identified 16 peptides with the desired activity: Angiotensins I, II, and III, and known fragments of these peptides. Using photo-induced cross-linking of unmodified proteins (PICUP), we identified 11 peptides with Aβ oligomerization inhibitory activity, including Angiotensins I-III. Thioflavin T fluorescence was used to identify 9 peptides with Aβ fibrillation inhibitory activity, including Angiotensins I-III. The discovery of these peptides contributes to the investigation of the mechanism underlying Alzheimer's disease pathology and the development of therapeutic strategies for Alzheimer’s disease.

Free Research Field

神経内科学