From the gut to the brain: is microbiome a new paradigm for Parkinson´s disease treatment?

• Autor(a) principal: Vilela, Cristiana Andreia Sousa
• Data de Publicação: 2023
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.22/24766
• topic: Parkinson’s Disease; Microbiome; Gut-Brain Axis; N-Acetyl cysteine

Parkinson's disease (PD) is recognized as the second most prevalent primary chronic neurodegenerative disorder of the Central Nervous System (CNS). Clinically, PD is characterized as a movement disorder, exhibiting an incidence and mortality rate that is increasing faster than any other neurological condition. In recent years, there has been a significant interest in investigating the role of the gut microbiome in the etiology and pathophysiology of PD. The establishment of a brain-gut microbiome axis is now real, with evidence denoting a bidirectional communication between the brain and the gut microbiota, which operates through various signaling pathways and mechanisms encompassing metabolic, immune, neuronal, and endocrine pathways. Among these, the vagus nerve represents the most direct form of communication. Given the intricate interactions between bacteria and drugs, it has been observed that treatments for PD can have an impact on the composition of the microbiome. Current treatments just provide effective management of motor symptoms and do not modify the course of the disease. For that, new routes have been considered, for instance, N-acetyl cysteine (NAC) is a naturally occurring molecule derived from the natural amino acid L-cysteine, associated with both antioxidant, mucolytic, and anti-inflammatory properties. It has demonstrated beneficial effects in modulating the symptomatology of PD, given that this medication is capable of restoring one of the major antioxidants of neurons, glutathione (GSH). Bearing this in mind, the main objective of the present project will be to understand if a real connection between the gut microbiome and PD exists and if the application of NAC has any influence on PD gut microbiota, thereby leading to cellular, molecular, and functional improvements. Such approach could open new therapeutical opportunities, leading to development of microbiome-based disease-modifying strategies for PD.