Autophagy in Spinocerebellar ataxia type 2, a dysregulated pathway, and a target for therapy.

Spinocerebellar ataxia type 2 (SCA2) is an incurable and genetic neurodegenerative disorder. The disease is characterized by progressive degeneration of several brain regions, resulting in severe motor and non-motor clinical manifestations. The mutation causing SCA2 disease is an abnormal expansion of CAG trinucleotide repeats in the ATXN2 gene, leading to a toxic expanded polyglutamine segment in the translated ataxin-2 protein. While the genetic cause is well established, the exact mechanisms behind neuronal death induced by mutant ataxin-2 are not yet completely understood. Thus, the goal of this study is to investigate the role of autophagy in SCA2 pathogenesis and investigate its suitability as a target for therapeutic intervention. For that, we developed and characterized a new striatal lentiviral mouse model that resembled several neuropathological hallmarks observed in SCA2 disease, including formation of aggregates, neuronal marker loss, cell death and neuroinflammation. In this new model, we analyzed autophagic markers, which were also analyzed in a SCA2 cellular model and in human post-mortem brain samples. Our results showed altered levels of SQSTM1 and LC3B in cells and tissues expressing mutant ataxin-2. Moreover, an abnormal accumulation of these markers was detected in SCA2 patients' striatum and cerebellum. Importantly, the molecular activation of autophagy, using the compound cordycepin, mitigated the phenotypic alterations observed in disease models. Overall, our study suggests an important role for autophagy in the context of SCA2 pathology, proposing that targeting this pathway could be a potential target to treat SCA2 patients.

A prática do controle social atraves dos conselhos de saúde / The pratice of social control through Health Councils

Uma ampla avaliacao da construcao da reforma sanitaria brasileira, implementada a partir dos anos 90, pela acao aguerrida dos novos atores -representantes de Secretarias Municipais e Estaduais de Saude, do Ministerio Publico, tecnicos, assessores e dirigentes de 1º escalao-, evidencia a persistencia e o acerto na construcao do SUS, como novo modelo assistencial. Embora o SUS ainda nao tenha cumprido integralmente sua vocacao de articulador da formacao profissional, vem enfrentando e vencendo desafios que enriquecem esse novo percurso de democratizacao, participacao e aprofundamento da reforma sanitaria brasileira. Importantes e significativos movimentos como a Rede UNIDA e o controle social atraves dos Conselhos de Saude sao frutos dessa reforma. Os Conselhos de Saude vem se configurando como novos coletivos, responsaveis pela construcao de uma nova cultura politica, que busca informacoes, analisa, avalia formula estrategias e controla a execucao das politicas de saude. As relacoes entre os Conselhos Estaduais de Saude os Conselhos Municipais e o Conselho Nacional de Saude vem se constituindo numa pratica bastante construtiva