20.3.13

First paper with drawings !

http://iospress.metapress.com/content/y05258137g173l5v/

Transforming Growth Factor β1 Modulates Amyloid β-Induced Glial Activation through the Smad3-Dependent Induction of MAPK Phosphatase-1

 B Flores and R von Bernhardi

 Chronic neuroinflammation has been proposed as a driving force for Alzheimer's disease (AD), which is characterized by amyloid-β (Aβ) deposition, neurofibrillary tangles, neuronal loss, and activation of glial cells. Persistent activation of mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB) pathway has been reported, which induces an increased expression of inflammatory mediators. Transforming growth factor β1 (TGFβ1) is an inflammation modulator whose levels are increased in AD. However, its canonical signaling pathway, Smad, appears to be impaired. Our previous findings indicate that TGFβ1 plays a key role in the pathogenesis of neuroinflammation, but the molecular mechanisms underlying its effects are not completely elucidated. Here, we studied the potential role of MKP-1, a phosphatase that exerts negative regulation on MAPK signaling, in the modulatory actions of TGFβ1. Using rat primary glial cultures, we found that pretreatment with TGFβ1 for 48 h reduced the production of inflammatory mediators induced by Aβ42, a result that was associated with prevention of MAPK p38 activation, attenuation of NF-κB p65 nuclear translocation, and an increase in MKP-1 levels. Moreover, suppression of MKP-1 expression by siRNA and inhibition of Smad3 reversed the modulation of inflammatory response exerted by TGFβ1. These results indicate that TGFβ1 induces the expression of MKP-1 in glial cells through the Smad pathway and inhibits MAPK and NF-κB signaling, thus revealing a novel mechanism for the neuroprotective actions of TGFβ1. Further research would be important in order to characterize the role of this mechanism in the pathogenesis of AD.

1.1.13

The dark side of the brain !!

Is the first publication of the year. So, we can start with a classic image and with a phrase of Elbert Hubband:
"The brain is a commodity used to fertilize ideas.”