Possible involvement of small oligomers of amyloid-beta peptides in 15-deoxy-delta 12,14 prostaglandin J2-sensitive microglial activation.

Abstract

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.

• Authors: Kazuyuki Takata, Yoshihisa Kitamura, Masaaki Umeki, Daiju Tsuchiya, Jun-ichi Kakimura, Takashi Taniguchi, Peter J Gebicke-Haerter, Shun Shimohama
• Journal: Journal of pharmacological sciences (J Pharmacol Sci) Vol. 91 Issue 4 Pg. 330-3 (Apr 2003) ISSN: 1347-8613 [Print] Japan
• PMID: 12719662 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 15-deoxy-delta(12,14)-prostaglandin J2
• Amyloid beta-Peptides
• Cytokines
• Nitrites
• Peptide Fragments
• amyloid beta-protein (1-40)
• amyloid beta-protein (1-42)
• Prostaglandin D2

Topics

• Amyloid beta-Peptides (pharmacology)
• Animals
• Brain (drug effects, metabolism)
• Cytokines (metabolism)
• Microglia (drug effects, metabolism)
• Nitrites (metabolism)
• Peptide Fragments (pharmacology)
• Prostaglandin D2 (analogs & derivatives, pharmacology)
• Rats
• Rats, Wistar