Among neurodegenerative disorders, Alzheimer’s disease (AD) represents the most common cause of dementia that can be seen through ageing. Senile plaques, neurofibrillary tangles and reactive gliosis are the most charateristic hallmarks of AD. Several factors are implicated in the development of this disease, comprehending genetic and environmental; among these, aging represents the prime risk factor in the development of AD. Until now, no effective treatments to prevent or delay this dementia are available. Sirtuins (SIRTs) rappresent a family of NAD+-dependent enzymes, in human divided in 7 different types, cluster in 4 classes according to phylogenetic analysis. Each of them has different function and localization, that allow them to control a multitude of biological processes. In this contest, SIRTs has already shown to be potentially able to modulate neurodegeneration with protective actions. Our hypothesis is that activation of SIRT1 or inhibition of SIRT2 would prevent reactive gliosis. Primary rat astrocytes were obteined by newborn Sprague-Dawely and activated with beta amyloid 1-42 (Aβ 1-42) and treated with resveratrol (RSV) or AGK-2, a SIRT1 activator and a SIRT2-selective inhibitor, respectively. Results confirmed that Aβ 1-42 peptides are able to affect cell vilability after 24 h treatment and to induce astrocyte proliferation observed after 72 h treatment. Both RSV and AGK-2 were able to control these events. Mostly, RSV and AGK-2 has shown to be able to reduce astrocyte activation, evaluated by the espression of GFAP and S100B, as well as the production of pro-inflammatory mediators like iNOS and COX-2. These data reveal novel findings about the therapeutic potential of SIRT modulators, and suggest novel strategies for AD treatment.
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|Titolo:||Sirtuins blunt reactive gliosis in an in vitro model of Alzheimer’s disease.|
BRONZUOLI, MARIA ROSANNA (Primo)
STEARDO, LUCA (Ultimo)
|Data di pubblicazione:||2014|
|Appartiene alla tipologia:||04d Abstract in atti di convegno|