Possible involvement of small oligomers of amyloid-beta peptides in 15-deoxy-delta 12,14 prostaglandin J2-sensitive microglial activation.
In Alzheimer's disease, fibrillar amyloid-beta (Abeta) peptides form senile plaques associated with microglia. However, the relationship between Abeta peptides and microglia is not fully understood. In this study, the incubation of Abeta1-40 (Abeta40) produced small oligomers, while incubation with Abeta1-42 (Abeta42) caused large molecular aggregates. Microglial production of nitrite, interleukin-6 and tumor necrosis factor-alpha was induced by Abeta40, but not Abeta42. This production was significantly reduced by 15-deoxy-Delta(12,14) prostaglandin J(2), and it was completely suppressed by beta-sheet breaker peptide, Leu-Pro-Phe-Phe-Asp. These results suggest that small oligomers, rather than large molecular aggregates, mediate microglial activation induced by Abeta peptides.
Department of Neurobiology, Kyoto Pharmaceutical University, Kyoto 607-8412, Japan.
Kazuyuki
K
Takata
Yoshihisa
Y
Kitamura
Masaaki
M
Umeki
Daiju
D
Tsuchiya
Jun-ichi
J
Kakimura
Takashi
T
Taniguchi
Peter J
PJ
Gebicke-Haerter
Shun
S
Shimohama
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D016229:Amyloid beta-Peptides; D016207:Cytokines; D009573:Nitrites; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D015230:Prostaglandin D2