RESUMEN

In recent years, proteasome involvement in the damage response induced by ionizing radiation (IR) became evident. However, whether proteasome plays a direct or indirect role in IR-induced damage response still unclear. Trypanosoma cruzi is a human parasite capable of remarkable high tolerance to IR, suggesting a highly efficient damage response system. Here, we investigate the role of T. cruzi proteasome in the damage response induced by IR. We exposed epimastigotes to high doses of gamma ray and we analyzed the expression and subcellular localization of several components of the ubiquitin-proteasome system. We show that proteasome inhibition increases IR-induced cell growth arrest and proteasome-mediated proteolysis is altered after parasite exposure. We observed nuclear accumulation of 19S and 20S proteasome subunits in response to IR treatments. Intriguingly, the dynamic of 19S particle nuclear accumulation was more similar to the dynamic observed for Rad51 nuclear translocation than the observed for 20S. In the other hand, 20S increase and nuclear translocation could be related with an increase of its regulator PA26 and high levels of proteasome-mediated proteolysis in vitro. The intersection between the opposed peaks of 19S and 20S protein levels was marked by nuclear accumulation of both 20S and 19S together with Ubiquitin, suggesting a role of ubiquitin-proteasome system in the nuclear protein turnover at the time. Our results revealed the importance of proteasome-mediated proteolysis in T. cruzi IR-induced damage response suggesting that proteasome is also involved in T. cruzi IR tolerance. Moreover, our data support the possible direct/signaling role of 19S in DNA damage repair. Based on these results, we speculate that spatial and temporal differences between the 19S particle and 20S proteasome controls proteasome multiple roles in IR damage response.

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Objetivo ­Verificar o papel dos polifenois na neuroproteção da DA. Métodos ­ Foram utilizados artigos originais relatados com experimentos "in vivo" em camundongos transgênicos em Inglês e Português, publicados entre 2007-2014 nas bases de dados Pubmed, Scielo e Lilacs. Resultados ­ Estudos evidenciaram que a administração oral de vários tipos de compostos polifenólicos mostraram o possível efeito protetor contra a DA em ratos transgênicos atuando sobre a inflamação causada por deposição de placa -amilóide, diminuindo a inflamação e evitando a progressão da DA. Conclusão ­ Conclui-se que os polifenóis administrados por via oral têm um papel neuroprotetor na DA, reduzindo a gravidade dos sintomas, contribuindo para a atenuação da progressão da doença.

Objective ­ To check polyphenols role in DA neuroprotection. Methods ­ Original articles reporting "in vivo" experiments on transgenic mice in English and Portuguese, published from 2007 to 2014 in Pubmed, Scielo and Lilacs databases. Results ­ Studies have found that oral administration of various types of polyphenolic compounds showed possible protective effect against AD in transgenic mice, by acting on the inflammation caused by deposition of -amyloid plaque, decreasing such inflammation and preventing the progression of AD. Conclusion ­ We conclude that polyphenols administered orally have a neuroprotective role on AD, mitigating the severity of the symptoms, and contributing to the attenuation of the progression of the disease.