1,3-Capryloyl-2-arachidonoyl glycerol activates alpha-secretase activity and suppresses Abeta40 secretion in A172 cells.
Alzheimer's disease (AD) is characterized by the deposition of amyloid beta-peptide (Abeta), derived from amyloid precursor protein (APP). Membrane states, such as lipid components or membrane fluidity, are important for enzymes related to APP processing in meeting their substrates efficiently. We analyzed the effects of triglycerides combined with polyunsaturated fatty acids (PUFAs) and/or caprylic acids on APP proteolysis. Our results showed that 1,3-capryloyl-2-arachidonoyl glycerol (8A8) moderately increased alpha-secretase activity (18%) in A172 cells. beta-Secretase activity was not statistically significantly changed in HEK293 cells stably expressing BACE1. However, Abeta40 secretion decreased by 22%. Thus, we conclude that 8A8 is a useful lipid compound for activating alpha-secretase activity and suppressing Abeta40 secretion.
Tanabe
Chiaki
C
Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo 153-8902, Japan.
Ebina
Maiko
M
Asai
Masashi
M
Futai
Eugene
E
Sasagawa
Noboru
N
Katano
Kenji
K
Fukami
Harukazu
H
Ishiura
Shoichi
S
D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology; D053829:Amyloid Precursor Protein Secretases / Q000187:drug effects* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D002210:Caprylates / Q000494:pharmacology*; D002460:Cell Line; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D005231:Fatty Acids, Unsaturated / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014280:Triglycerides / Q000494:pharmacology*
C539983:1,3-capryloyl-2-arachidonoyl glycerol; D016229:Amyloid beta-Peptides; D002210:Caprylates; D005231:Fatty Acids, Unsaturated; D010446:Peptide Fragments; D014280:Triglycerides; C078592:amyloid beta-protein (1-40); D053829:Amyloid Precursor Protein Secretases