Testing the application of new chemical formulations for neurological disease therapies

• Autor(a) principal: David, Emanuel Silva
• Data de Publicação: 2018
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.6/9788
• topic: Antioxidantes; Doença de Parkinson; Líquidos Iónicos; Neurónios Dopaminérgicos; Stress Oxidativo; Domínio/Área Científica::Ciências Naturais::Ciências Químicas

Parkinson’s Disease (PD) is a multifactorial neurodegenerative disease, characterised by a decrease in the dopamine levels released by the dopaminergic neurons, the formation of Lewis bodies, formed mainly by a-synuclein and by the death of dopaminergic neurons of the substantia nigra. Several different mechanisms are dysregulated in Parkinson’s disease such as the inflammatory process; the dysfunction of mitochondria; the synthesis and degradation of dopamine and the activation of NADPH oxidases, all resulting in the production of reactive oxygen species (ROS) in large quantity which originates a highly oxidative environment in the dopaminergic neurons. Given the high importance of oxidative stress in Parkinson’s Disease, it is of particular interest the use of antioxidants in the treatment of this disease, such as vanillic acid, syringic acid and salicylic acid. However, these compounds present low solubility and low bioavailability which makes impracticable their use in the treatment of Parkinson’s Disease. Thus, in this thesis, new formulations of cholinium-based ionic liquids were used in order to increase the solubility and therefore the bioavailability od these compounds. For each ILs based antioxidant and its respective precursor, cytotoxicity and neuroprotection tests were performed in the dopaminergic neurons cell line (N27). The obtained results disclosed that vanillic acid, syringic acid, salicylic acid, cholinium vanillate, cholinium syringate and cholinium salicylate do not present cytotoxicity to dopaminergic neurons. Furthermore, it was also possible to conclude that none of the tested compounds (precursors and respective ionic liquids) exhibited neuroprotective characteristics in the three different in vitro models of PD tested.