Mitochondrial Dysfunction: The Road to Alpha-Synuclein Oligomerization in PD.

While the etiology of Parkinson's disease remains largely elusive, there is accumulating evidence suggesting that mitochondrial dysfunction occurs prior to the onset of symptoms in Parkinson's disease. Mitochondria are remarkably primed to play a vital role in neuronal cell survival since they are key regulators of energy metabolism (as ATP producers), of intracellular calcium homeostasis, of NAD(+)/NADH ratio, and of endogenous reactive oxygen species production and programmed cell death. In this paper, we focus on mitochondrial dysfunction-mediated alpha-synuclein aggregation. We highlight some of the findings that provide proof of evidence for a mitochondrial metabolism control in Parkinson's disease, namely, mitochondrial regulation of microtubule-dependent cellular traffic and autophagic lysosomal pathway. The knowledge that microtubule alterations may lead to autophagic deficiency and may compromise the cellular degradation mechanisms that culminate in the progressive accumulation of aberrant protein aggregates shields new insights to the way we address Parkinson's disease. In line with this knowledge, an innovative window for new therapeutic strategies aimed to restore microtubule network may be unlocked.

Mitochondria: the common upstream driver of amyloid-ß and tau pathology in Alzheimer's disease.

Mitochondrial dysfunction has been widely implicated in the etiology of Alzheimer's disease (AD). Evidence shows a mitochondrial-mediated impairment of autophagy that potentiates amyloid-ß (Aß) deposition. Accordingly, recent data obtained from AD models, in which mitochondrial alterations are a prominent feature, demonstrated abnormalities in microtubule network, involving tubulin and tau post-translational modifications. In this review we will discuss mitochondrial-regulated processes where mitochondrial malfunction is likely to start a sequence of events leading to sirtuin-2 activation, microtubule network breakdown, and impairment of the autophagic pathway. Because sirtuin-2 activity depends on cellular NAD+ availability, mitochondrial regulation of NAD+ levels may contribute to an increase in sirtuin-mediated tubulin deacetylation. A vicious cycle become installed which potentiates tau hyperphosphorylation, together with Aß overproduction and deposition. Overall, targeting microtubule network constitutes a promising strategy for pharmacological therapy in AD.

Substituição parcial de farelo de soja por ureia protegida na produção e composição do leite / Effects of partial replacement of soybean meal by protected urea on milk yield and composition

Avaliaram-se os efeitos da ureia protegida na produção e composição do leite, utilizando-se 34 vacas da raça Holandesa, com 128±60 dias em leite e produção de 41,6±6,7kg/dia no início do experimento, distribuídas em blocos por produção de leite, ordem de lactação e dias em lactação. As variáveis produção de leite, porcentagens e produções de gordura, proteína, lactose e sólidos totais do leite, contagem de células somáticas e nitrogênio ureico no leite foram mensuradas aos 30 e 60 dias do experimento. Os dados foram analisados por procedimento de modelos mistos com o modelo contendo como covariável as observações obtidas antes da adoção das dietas experimentais e os efeitos fixos de período, de tratamento e a interação de período versus tratamento. Os tratamentos (T) foram compostos por dietas isoenergéticas e isonitrogenadas com 1,66 EL L e 18,35 por cento de PB, definidas como: T1= 11,4 por cento farelo de soja e T2= 0,4 por cento ureia encapsulada + 9,0 por cento farelo de soja. Não foram observadas diferenças (P>0,05) nas produções diárias de leite e de sólidos, de nitrogênio ureico no leite e da contagem de células somáticas. A dieta com ureia protegida reduziu (P<0,05) as porcentagens de gordura e de sólidos totais do leite. A substituição parcial do farelo de soja por ureia protegida não reduziu o desempenho produtivo das vacas em lactação.

The effects of protected urea on milk yield and composition were evaluated. Thirty-four lactating Holstein cows, with 128±60 days in milk and yield of 41.6±6.7 kg/day at the beginning of the trial, were blocked by milk production, lactation number, and days in milk. Milk yield; yields and contents of fat, protein, lactose, total solids; somatic cell count; and milk urea nitrogen were measured on days 30 and 60 of the comparison period. Variables measured before the application of treatments were used as covariate in the statistical model. Data were analyzed with the mixed procedure of SAS with a model containing the continuous effect of the covariate and the fixed effects of period, treatment, and the interaction of period and treatment. Treatments (T) were isoenergetic and isonitrogenous diets with 1.66 EL L and 18.35 percent of CP, described as: T1= 11.4 percent soybean meal and T2= 0.4 percent encapsulated urea + 9.0 percent soybean meal. There was no treatment effect (P>0.05) on the daily production of milk and solids, milk urea nitrogen, and somatic cell count. The slow release urea diet reduced (P<0.05) milk fat and total solids contents. The partial replacement of soybean meal by protected urea did not decrease the performance of lactating cows.