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.

No abstract

Sustainability of cork oak (Quercus suber) forests is threatened by biotic and abiotic factors and characterization of potentially differing genetic resources has therefore gained importance. This work addresses the chemical variation of the three tissues of cork oak stems – cork, phloem and wood – in relation to tree and provenance, looking for genetic chemical diversity and for physiological derived differences. The three tissues differ with cork clearly differentiating regarding summative composition, component ratios and monomeric composition. Cork is the only tissue where suberin is present (42.3% o.d. mass) as the main cell wall component, and it has a high content of extractives (11.7%) with significant proportion of lipophilic compounds. Phloem is more lignified than wood (38.0% vs. 23.4%) and has less polysaccharides (49.1% vs. 64.6%) with glucose-to-other sugars relation of 1:1.3 in phloem and 1:0.7 in wood. Analytical pyrolysis showed that lignification is a heterogeneous process and the lignin monomeric composition depends on tissue and cell type: cork lignin has a H:G:S ratio of 1:2.5:0.3 and S/G ratio of 0.12, while phloem and wood lignins have mainly G and S units with a S/G ratio of respectively 1.1 and 2.3. No significant differences were found between the three provenances, but some chemical variation occurred between the trees within a provenance. NIR spectroscopy and principal component analysis differentiated cork, phloem and wood, while the dispersion within each group highlighted the significant tree variability, while provenances were a non-significant factor of chemical variation.

No abstract