التفاصيل البيبلوغرافية
| العنوان: |
Modulation of Lipid Kinase PI4KIIα Activity and Lipid Raft Association of Presenilin 1 Underlies γ-Secretase Inhibition by Ginsenoside (20S)-Rg3. |
| المؤلفون: |
Min Suk Kang1, Seung-Hoon Baek2, Yoon Sun Chun3, Zenobia Moore, A.1, Landman, Natalie1, Berman, Diego1, Hyun Ok Yang4, Maho Morishima-Kawashima5, Satoko Osawa6, Satoru Funamoto7, Yasuo Ihara7, Di Paolo, Gilbert1, Jeong Hill Park8, Sungkwon Chung3 schung@skku.edu, Kim, Tae-Wan1 twk16@columbia.edu |
| المصدر: |
Journal of Biological Chemistry. 7/19/2013, Vol. 288 Issue 29, p20868-20882. 15p. |
| مصطلحات موضوعية: |
*LIPID metabolism, *PRESENILINS, *MEMBRANE proteins, *SECRETASES, *GINSENOSIDES, *LABORATORY mice, *PHOSPHATIDYLINOSITOL 3-kinases |
| مستخلص: |
Amyloid β-peptide (Aβ) pathology is an invariant feature of Alzheimer disease, preceding any detectable clinical symptoms by more than a decade. To this end, we seek to identify agents that can reduceAβ levels in the brain via novel mechanisms.We found that (20S)-Rg3, a triterpene natural compound known as ginsenoside, reducedAβ levels in cultured primary neurons and in the brains of a mouse model of Alzheimer disease. The (20S)- Rg3 treatment induced a decrease in the association of presenilin 1 (PS1) fragments with lipid rafts where catalytic components of the γ-secretase complex are enriched. TheAβ-lowering activity of (20S)-Rg3 directly correlated with increased activity of phosphatidylinositol 4-kinase IIα (PI4KIIα), a lipid kinase that mediates the rate-limiting step in phosphatidylinositol 4,5-bisphosphate synthesis. PI4KIIα overexpression recapitulated the effects of (20S)-Rg3, whereas reduced expression of PI4KIIα abolished theAβ-reducing activity of (20S)-Rg3 in neurons. Our results substantiate an important role for PI4KIIα and phosphoinositide modulation in γ-secretase activity and Aβ biogenesis. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
Academic Search Index |
Full Text Finder