|
|
Hokkaido University Collection of Scholarly and Academic Papers >
Faculty of Pharmaceutical Sciences >
Peer-reviewed Journal Articles, etc >
Suppression of amyloid-β secretion from neurons by cis-9, trans-11-octadecadienoic acid, an isomer of conjugated linoleic acid
| Title: | Suppression of amyloid-β secretion from neurons by cis-9, trans-11-octadecadienoic acid, an isomer of conjugated linoleic acid |
| Authors: | Hata, Saori Browse this author →KAKEN DB | | Kikuchi, Kazunori Browse this author | | Kano, Kuniyuki Browse this author | | Saito, Haruka Browse this author | | Sobu, Yuriko Browse this author | | Kinoshita, Shoichi Browse this author | | Saito, Takashi Browse this author | | Saido, Takaomi C. Browse this author | | Sano, Yoshitake Browse this author | | Taru, Hidenori Browse this author →KAKEN DB | | Aoki, Junken Browse this author | | Komano, Hiroto Browse this author | | Tomita, Taisuke Browse this author | | Natori, Shunji Browse this author | | Suzuki, Toshiharu Browse this author →KAKEN DB |
| Keywords: | Alzheimer's disease | | amyloid-beta | | APP | | BACE1 | | conjugated linoleic acid |
| Issue Date: | 11-Aug-2021 |
| Publisher: | John Wiley & Sons |
| Journal Title: | Journal of neurochemistry |
| Volume: | 159 |
| Issue: | 3 |
| Start Page: | 603 |
| End Page: | 617 |
| Publisher DOI: | 10.1111/jnc.15490 |
| Abstract: | Two common conjugated linoleic acids (LAs), cis-9, trans-11 CLA (c9,t11 CLA) and trans-10, cis-12 CLA (t10,c12 CLA), exert various biological activities. However, the effect of CLA on the generation of neurotoxic amyloid-beta (A beta) protein remains unclear. We found that c9,t11 CLA significantly suppressed the generation of A beta in mouse neurons. CLA treatment did not affect the level of beta-site APP-cleaving enzyme 1 (BACE1), a component of active gamma-secretase complex presenilin 1 amino-terminal fragment, or A beta protein precursor (APP) in cultured neurons. BACE1 and gamma-secretase activities were not directly affected by c9,t11 CLA. Localization of BACE1 and APP in early endosomes increased in neurons treated with c9,t11 CLA; concomitantly, the localization of both proteins was reduced in late endosomes, the predominant site of APP cleavage by BACE1. The level of CLA-containing phosphatidylcholine (CLA-PC) increased dramatically in neurons incubated with CLA. Incorporation of phospholipids containing c9,t11 CLA, but not t10,c12 CLA, into the membrane may affect the localization of some membrane-associated proteins in intracellular membrane compartments. Thus, in neurons treated with c9,t11 CLA, reduced colocalization of APP with BACE1 in late endosomes may decrease APP cleavage by BACE1 and subsequent A beta generation. Our findings suggest that the accumulation of c9,t11 CLA-PC/LPC in neuronal membranes suppresses the production of neurotoxic A beta in neurons. |
| Rights: | This is the peer reviewed version of the following article: https://onlinelibrary.wiley.com/doi/10.1111/jnc.15490, which has been published in final form at 10.1111/jnc.15490. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited. |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/86603 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
|
Submitter: 鈴木 利治
|
