Investigação do efeito neuroprotetor da atorvastatina em um modelo in vitro de toxicidade induzida pelo peptídeo ¿-amiloide

AUTOR(ES)

Thaline da Silva

FONTE

IBICT - Instituto Brasileiro de Informação em Ciência e Tecnologia

DATA DE PUBLICAÇÃO

2012

RESUMO

Alzheimer¿s disease is an age-related neurodegenerative disorder characterized by progressive memory loss, inability to perform the activities of daily living and personality changes. AD is characterized histopathologically by the presence of senile plaques, neurofibrillary tangles, synapse loss and neuronal death. Moreover, it is now recognized that neuroinflammation is a proeminent feature of Alzheimer¿s disease brain, with inflammatory responses playing a significant role in modulating disease progression. Unfortunately, drugs effective for this disease are limited to acetylcholinesterase inhibitors that do not impact disease pathogenesis. Statins, which belong to the class of cholesterol-reducing drugs, were proposed as novel agents useful in AD therapy due the neuroprotective and anti-inflammatory properties that they have. In this study, we evaluated the neuroprotective effect of atorvastatin, a HMG-CoA reductase inhibitor, against A¿25-35 peptide induced toxicity in organotypic hippocampal slice cultures. The cultures were treated with 2.5¿M or 5¿M of atorvastatin and then exposed to 25¿M of A¿25-35 for 48h. We also investigated the involvement of PI3K signaling pathway, oxidative responses, astroglial activation, and synaptophysin (pre-synaptic marker) and cytokines levels on the atorvastatin protection against ¿-amyloid-induced toxicity. Atorvastatin treatment prevented the cell damage induced by the exposure to peptide A¿25-35, reduced inflammatory and oxidative responses and increased the immunocontent of synaptophysin. In addition, atorvastatin significantly prevented the activation of GSK-3¿, the astroglial activation and the ¿-amyloid-induced increase in TNF-¿ and IL-6 levels. Taken together, these observations suggest that atorvastatin may provide an effective neuroprotective action against neurotoxicity induced by A¿ through the activation of the PI3K/AKT signaling pathway and attenuation of oxidative responses and neuroinflammation, and could be a potencial drug used on Alzheimer disease.

ASSUNTO(S)

doença de alzheimer inibidores de hidroximetilglutaril-coa redutases atorvastatina neuroproteção

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