Abstract
Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder. Accumulating data indicate that astrocytes play an important role in the neuroinflammation related to the pathogenesis of AD. It has been shown that microglia and astrocytes are activated in AD brain and amyloid-β (Aβ) can increase the expression of cyclooxygenase 2 (COX-2), interleukin-1, and interleukin-6. Suppressing the inflammatory response caused by activated astrocytes may help to inhibit the development of AD. Curcumin is a major constituent of the yellow curry spice turmeric and proved to be a potential anti-inflammatory drug in arthritis and colitis. There is a low age-adjusted prevalence of AD in India, a country where turmeric powder is commonly used as a culinary compound. Curcumin has been shown to suppress activated astroglia in amyloid-β protein precursor transgenic mice. The real mechanism by which curcumin inhibits activated astroglia is poorly understood. Here we report that the expression of COX-2 and glial fibrillary acidic protein were enhanced and that of peroxisome proliferator-activated receptor γ (PPARγ) was decreased in Aβ25-35-treated astrocytes. In line with these results, nuclear factor-κB translocation was increased in the presence of Aβ. All these can be reversed by the pretreatment of curcumin. Furthermore, GW9662, a PPARγ antagonist, can abolish the anti-inflammatory effect of curcumin. These results show that curcumin might act as a PPARγ agonist to inhibit the inflammation in Aβ-treated astrocytes.