Microsomal prostaglandin E synthase-1 is induced in alzheimer's disease and its deletion mitigates alzheimer's disease-like pathology in a mouse model.

Abstract

Epidemiological studies have suggested that long-term use of nonsteroidal anti-inflammatory drugs that inhibit cyclooxygenase (COX) activity can moderate the onset or progression of Alzheimer's disease (AD). Thus it has been suggested that prostaglandin E2 (PGE2 ), a major end-product of COX, may play a pathogenic role in AD, but the involvement of PGE synthase (PGES), a terminal enzyme downstream from COX, has not been fully elucidated. Here we found that, among three PGES enzymes, only microsomal PGES-1 (mPGES-1) is induced, and its expression is associated with β-amyloid (Aβ) plaques in the cerebral cortex in human AD patients and in Tg2576 mice, a transgenic AD mouse model. Furthermore, to investigate whether mPGES-1 contributes to AD-like pathology, we bred mPGES-1-deficient mice with Tg2576 mice. We found that mPGES-1 deletion reduced the accumulation of microglia around senile plaques and attenuated learning impairments in Tg2576 mice. These results indicated that mPGES-1 is induced in the AD brain and thus plays a role in AD pathology. Blockage of mPGES-1 could form the basis for a novel therapeutic strategy for patients with AD.

• Authors: Yoshiharu Akitake, Yoshihito Nakatani, Daisuke Kamei, Masato Hosokawa, Hiroyasu Akatsu, Satoshi Uematsu, Shizuo Akira, Ichiro Kudo, Shuntaro Hara, Mitsuo Takahashi
• Journal: Journal of neuroscience research (J Neurosci Res) Vol. 91 Issue 7 Pg. 909-19 (Jul 2013) ISSN: 1097-4547 [Electronic] United States
• PMID: 23553915 (Publication Type: Journal Article)
• Copyright: Copyright © 2013 Wiley Periodicals, Inc.

Chemical References

• Amyloid beta-Protein Precursor
• Intramolecular Oxidoreductases
• PTGES protein, human
• Prostaglandin-E Synthases
• Ptges protein, mouse

Topics

• Aged
• Aged, 80 and over
• Alzheimer Disease (enzymology, genetics, pathology)
• Amyloid beta-Protein Precursor (genetics)
• Animals
• Case-Control Studies
• Cerebral Cortex (enzymology)
• Disease Models, Animal
• Female
• Gene Expression Regulation, Enzymologic (genetics)
• Humans
• Intramolecular Oxidoreductases (deficiency, genetics)
• Male
• Maze Learning (physiology)
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Plaque, Amyloid (metabolism, pathology)
• Prostaglandin-E Synthases