Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by a selective loss of upper and lower motor neurons. Recent studies have shown that mutations in SQSTM1 are linked to ALS. SQSTM1 encodes SQSTM1/p62 that regulates not only autophagy via the association with MAP1LC3/LC3 and ubiquitinated proteins but also the KEAP1-NFE2L2/Nrf2 anti-oxidative stress pathway by interacting with KEAP1. Previously, we have demonstrated that loss of SQSTM1 exacerbates disease phenotypes in a SOD1H46R-expressing ALS mouse model. To clarify the effects of SQSTM1 overexpression in this model, we generated SQSTM1 and SOD1H46R double-transgenic (SQSTM1;SOD1H46R) mice. SQSTM1;SOD1H46R mice exhibited earlier disease onset and shorter lifespan than did SOD1H46R mice. Conversely, disease progression after the onset rather slightly but significantly slowed in SQSTM1;SOD1H46R mice. However, there were observable differences neither in the number of Nissl positive neurons nor in the distribution of ubiquitin-positive and/or SQSTM1-positive aggregates between SOD1H46R and SQSTM1;SOD1H46R mice. It was noted that these protein aggregates were mainly observed in neuropil, and partly localized to astrocytes and/or microglia, but not to MAP2-positive neuronal cell bodies and dendrites at the end-stage of disease. Nonetheless, the biochemically-detectable insoluble SQSTM1 and poly-ubiquitinated proteins were significantly and progressively increased in the spinal cord of SQSTM1;SOD1H46R mice compared to SOD1H46R mice. These results suggest that overexpression of SQSTM1 in SOD1H46R mice accelerates disease onset by compromising the protein degradation pathways.Electronic supplementary materialThe online version of this article (10.1186/s13041-018-0373-8) contains supplementary material, which is available to authorized users.

Este trabalho verificou o efeito dos óleos essenciais (OE) extraídos de Eremanthus erythropappus (candeia), Cymbopogon martinii (palmarosa) e de Rosmarinus officinalis (alecrim) no crescimento micelial de alguns fitopatógenos fúngicos e no tratamento de sementes de milho, soja e feijão. No teste in vitro, alíquotas de 20, 40, 60, 100, 200, 500 e 1000 μL de cada um dos óleos essenciais foram distribuídas na superfície do meio de cultura. Posteriormente, discos de meio de cultura com micélio de Alternaria carthami, Alternaria sp. e Rhizoctonia solani foram transferidos para o centro de cada placa. O crescimento foi mensurado e calculada a taxa de inibição do crescimento micelial (ICM). Para verificar o efeito dos OE na germinação das sementes utilizou-se a aplicação deles por fumigação. Foi avaliada a percentagem de sementes germinadas e a incidência de patógenos nas sementes. Sobre o crescimento micelial, o óleo de palmarosa inibiu completamente todos os patógenos fúngicos, independentemente da concentração. Já os óleos de candeia e alecrim foram melhores quando foram adicionadas alíquotas superiores a 200 μL. Os óleos influenciaram diferentemente a germinação e a sanidade das sementes de milho, soja e feijão.

We explored the possibility of the cysteinyl leukotriene receptor antagonists, pranlukast and montelukast, preventing tumor cell migration through both cerebral and peripheral capillaries. To study tumor cell migration through brain capillaries, male Fisher rats were cannulated via the cisterna magna under pentobarbital anesthesia. RCN9 cells labeled with a fluorescent marker PKH67 were intravenously administered following arachidonic acid administration into the subarachnoid space, and specimens of the central nervous system were collected every 30 min for 8 h. Arachidonic acid increased the fluid volume with elevated white blood cell and RCN9 cell counts. When given 2 h before arachidonic acid administration, pranlukast, but not montelukast, reduced the fluid volume and inhibited white blood cell and RCN9 cell extravasation through the brain capillary. In addition, a Lewis lung carcinoma metastasis model in mice was used to study the inhibitory effect of pranlukast and montelukast against cancer cell extravasation through general capillaries. When mice were given food containing either pranlukast or montelukast, immediately after paw amputation, tumor metastasis was prevented by both drugs, and their survival was prolonged. These results show that pranlukast can inhibit tumor cell migration through both the brain and peripheral capillaries, whereas montelukast inhibits tumor cell migration only in the peripheral capillaries.

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