By 2040, the World Health Organization expects neurodegenerative diseases, such as Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), and Parkinson’s disease, to surpass cancer as the second most common cause of death worldwide. Currently, only treatments for symptoms of these diseases are available. Thus, research is critical to alleviate this public health burden by elucidating the pathogenic processes and developing novel therapies. While exact mechanisms by which these heterogeneous neuropathological conditions become manifest in patients remain unclear, growing evidence suggests that oxidative stress (OS) makes a significant contribution to neuronal dysfunction and apoptosis in all major neurodegenerative diseases. Recently, the gene oxidation resistance 1 (Oxr1) has emerged as a critical regulator of neuronal survival in response to OS. Oxr1 is expressed throughout the central nervous system, and its highly conserved TLDc domain protects neurons from oxidative damage through an unknown mechanism. This thesis aimed to define mechanisms by which Oxr1 confers neuronal sensitivity to OS, and to determine its role in neurodegenerative diseases. I found that Oxr1 mediates cytoplasmic localization of ALS-associated proteins Fused in Sarcoma (FUS) and transactive response DNA binding protein 43 kDa (TDP-43) through a TLDc domain- and arginine methylation-dependent pathway. Next, I investigated in vivo neuroprotective functions of Oxr1, and demonstrated that neuronal Oxr1 over-expression extends survival and ameliorates behavioural dysfunction and pathology of an ALS mouse model. In particular, neuronal Oxr1 over-expression strikingly delays neuroinflammation during ALS pathogenesis. Finally, I characterised a mouse model that specifically deletes Oxr1 from motor neurons. While loss of Oxr1 in ChAT-positive motor neurons does not cause overt neurodegeneration in the spinal cord, constitutive loss of Oxr1 leads to neuroinflammation in the cerebellum and spinal cord. Taken together, these studies illuminate functions of Oxr1 in the complex antioxidant defence network and present implications for future therapeutic strategies.

Zr-Si-N thin films were deposited by reactive magnetron sputtering to study silicon influence in the structure, morphology and properties such as hardness and oxidation resistance. Six thin films with silicon concentrations from 2.8 to 14.9 at.% were selected. Thin films morphology shows that there are no columnar grains, structure that is commonly observed in films deposited by sputtering. It was identified amorphous and crystalline areas in films microstructure, creating a structure composed by crystalline grains embedded in an amorphous phase, which were characterized by EDS as Zr and Si rich areas, respectively. XRD results indicate ZrN peaks intensity reduction and a broadening increase due silicon nitride segregation to grain boundaries, which is responsible for grain size reduction, that was calculated by Scherrer and reached magnitudes lower than 10 nm. XRD peaks displacement are observed for all samples and it can be explained due formation of a solid solution in which Si replaces Zr atoms in ZrN crystal lattice and due a strong interface between crystalline phase and amorphous one. XPS data reinforce the presence of compounds like ZrN and Si3N4 and it is also possible to infer the formation of a solid solution of Si in ZrN lattice. Oxidation tests were performed at temperatures in the range of 500°C to 1100°C. ZrN film is almost fully oxidized at 500°C, while films with high silicon content maintain ZrN grains stable at 700°C. When oxidized, ZrN films form monoclinic ZrO2 phase, but, in films with silicon addition, the stable phase is the tetragonal one. This happens due ZrN grain size reduction, because tetragonal phase has the lowest surface energy. Oxidation tests results confirm that there is a mechanism acting as diffusion barrier in films, preventing grains coalescence and oxygen diffusion into film structure. This mechanism is a direct consequence of silicon segregation process to grain boundaries, which ensures the formation of a nanostructure composed of ZrN grains embedded by an amorphous Si3N4 layer (nc-ZrN/a-Si3N4), allowing oxidation resistance improvement in at least 200°C. / Filmes finos de Zr-Si-N foram depositados por magnetron sputerring reativo para estudar a influência do teor de silício na estrutura, morfologia e propriedades como dureza e resistência a oxidação. Para tal, foram selecionados seis filmes com teor de Si entre 2,8 e 14,9 at.%. A morfologia demonstra que a estrutura colunar característica dos filmes depositados por sputtering não existe. A estrutura é composta por áreas cristalinas e outras amorfas, na qual os grãos cristalinos estão envolvidos pela fase amorfa, sendo que EDS detectou que estas fases são ricas em Zr e Si, respectivamente. Há redução de intensidade e alargamento dos picos de difração do ZrN, efeito provocado pela segregação do Si3N4 para região dos contornos, fato que propicia a redução do tamanho de grão, o qual foi calculado por Scherrer e atinge magnitude inferior a 10 nm. Os picos do DRX estão deslocados, fato justificado pela formação de uma solução sólida na qual o Si substituiu o Zr no reticulado do ZrN e pela forte interface formada entre as fases cristalina e amorfa. Dados de XPS reforçam a formação de uma estrutura bifásica de ZrN e Si3N4 e mostra indícios de que há uma solução sólida de Si no ZrN. Os ensaios de oxidação foram realizados em temperaturas de 500°C até 1100°C. O filme de ZrN praticamente se oxida a 500°C, enquanto nos filmes com altos teores de silício os grãos de ZrN se mantém estáveis até 700°C. Quando oxidado, os filmes de ZrN formam predominantemente ZrO2 na fase monoclínica, mas, nos filmes com adição de Si há a inversão para a fase tetragonal. Tal fato é fruto da redução do tamanho de grão, pois a fase tetragonal possui menor energia de superfície. Tais resultados ratificam que existe mecanismo atuando como barreira a difusão, o qual impede a coalescência dos grãos e a difusão do oxigênio. Este mecanismo é resultado do processo de segregação do silício para os contornos, o qual assegura a formação da nanoestrutura composta de grãos de ZrN embebidos por camada amorfa de Si3N4 (nc- ZrN/a-Si3N4) e permite aprimorar a resistência a oxidação em pelo menos 200°C.

Carbon fiber (CF) must be protected from thermal oxidation for high temperature application because of its low thermo-oxidative stability above 450°C in air. CF is now increasingly being used as a reinforcing material in the construction industry. A thermal and oxidation resistant coating is necessary for CF-reinforced concrete (CFRC) composites in order to satisfy a high level of safety standard in the case of fire. New types of pre-ceramic coatings, such as Tyranno® polymer (Si–Ti based pre-ceramic) and SiO₂ sol–gel, have been deposited on CF filament yarn by means of a wet chemical continuous dip coating method. The results of surface analyses, e.g. scanning electron microscopy, X-ray photoelectron spectroscopy, and infrared spectroscopy, showed the changes in topographical properties of CF caused by the coatings. Thermogravimetric analysis proved that the high temperature (up to 800°C) oxidation stability of CF was considerably improved due to the coatings. Tensile test results indicated that the strength of CF yarn at 20°C was increased by up to 80% with the coatings. Thermo-mechanical properties were also enhanced up to 600°C. CF yarn retains its original strength and elasticity modulus, i.e. the stiffness at 700°C, with a Tyranno® polymer coating.