Intramembrane proteolysis of beta-APP in a gamma-secretase independent mechanism

2017 Fiscal Year Final Research Report

• Project/Area Number: 26461745
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Osaka University
• Principal Investigator: Yanagida Kanta 大阪大学, 医学系研究科, 特任研究員(常勤) (70467596)
• Co-Investigator(Kenkyū-buntansha): 田上 真次 大阪大学, 医学系研究科, 助教 (40362735) ; 大河内 正康 大阪大学, 医学系研究科, 講師 (90335357)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Keywords: アルツハイマー病 / γ-セクレターゼ / CRISPR/CAS9

Outline of Final Research Achievements

To investigate the γ-secretase independent intramembrane cleavage mechanism of amyloid β precursor protein (βAPP), we generated presenilin 1 and presenilin 2 double knockout (PSDKO) cells by CRISPR/Cas9 system. PSDKO cells were treated with various protease inhibitors and intracellular oligopeptides derived from transmembrane domain of βAPP were quantified by LC-Ms/Ms. As a result, eight tripeptides were decreased by treatment of lysosomal enzyme inhibitor chloroquine. Since these peptides were not decreased by inhibition of cathepsins, the major lysosomal proteases, it was suggested that intramembrane domain of βAPP was degraded by tripeptidyl peptidase 1, which releases tripeptides from N-termini of proteins.

Free Research Field

アルツハイマー病