Safinamide Therapeutical Effects: Seeking for a disease-modifying strategy for Parkinson's Disease

• Autor(a) principal: Vitorino Gomes Dias
• Data de Publicação: 2023
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
• Texto Completo: https://hdl.handle.net/10216/157184
• topic: Ciências médicas e da saúde; Medical and Health sciences

Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by motor and non-motor symptoms, resulting from the degeneration of a specific neuronal population, the dopaminergic neurons at the level of the substantia nigra. Currently, PD subsists without a cure, presenting a whole portfolio of pharmacological and surgical treatments that only temporarily alleviate the associated motor symptoms, not preventing its progression. New concepts have been introduced based on the development of multimodal compounds that can promote a multi-target approach. In this perspective, safinamide (an inhibitor of the enzyme monoamine oxidase B) is an approved drug for the treatment of PD, containing dopaminergic and non-dopaminergic multimodal actions. However, in the field of non-dopaminergic activities, the effects of safinamide remain unknown. Thus, the present thesis aimed to evaluate the impact of safinamide on the modulation of neuroinflammation and metabolic-molecular pathways in an animal model of PD (6-hydroxydopamine (6-OHDA)). From the results obtained, we verified that safinamide is a modulator of neuroinflammation since a significant decrease was observed in microglial cells (CD11b-positive staining) compared to the untreated group (6-OHDA). Additionally, we verified that safinamide is also a potential modulator of oxidative stress and autophagic processes since, after its application, the expression of PARK7, LC3B, and SOD1 was altered. Therefore, this work opens new perspectives for the application of safinamide since this drug is only approved as an adjuvant therapy to levodopa and was never used as a monotherapy in clinical practice. Additionally, we demonstrate for the first time that safinamide appears to impact the modulation of antioxidant molecules, opening new perspectives for its application as a disease-modifying agent to be considered for the early stages of PD.