O receptor P2X7 e a via de PGC-1A/PPAR como alvos na estratégia do desenvolvimento de terapias para a doença de Parkinson

• Autor(a) principal: Ferrazoli, Enéas Galdini [UNIFESP]
• Data de Publicação: 2017
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Repositório Institucional da UNIFESP
• Texto Completo: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=5454125; http://repositorio.unifesp.br/handle/11600/49934
• topic: Parkinson Disease; Brilliant Blue F; Pgc 1 Alpha; Fenofibrate; Neural Progenitor Cells; Doença de Parkinson; Brilliant Blue G (BBG); Pgc-1alfa; Fenofibrato; Células progenitoras neurais; Receptor P2X7

Parkinson's Disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra and their projections to the striatum, and there are no therapies that significantly delay its progression so far. Currently, the most common treatment for PD is the administration of Levodopa, but this drug has limited efficacy and many side effects, such as dyskinesias. Recently, several groups have demonstrated the participation of purinergic receptors, especially the P2X7 receptor (P2X7R), and the peroxisome proliferator activated receptor (PPAR), in neuroinflammatory and neurodegenerative pathways, suggesting that these might be important targets for therapies for neurodegenerative diseases. It is also known that the inflammation process is closely linked to the mechanisms of neuronal death in PD. Further, neural stem / progenitor cells express various chemokines and chemokine receptors that are involved in the homing of these cells to sites of injury in the central nervous system; thus transplantation of neural stem / progenitor cells is indicated as a promising strategy for the treatment of neurodegenerative diseases. The objective of the present study was to evaluate the therapeutic effect of the use of the P2X7R blocker Brilliant Blue G, the PPAR activator fenofibrate, and neural progenitor cell transplantation in an in vitro model for PD. For this purpose, we used the hemiparkinsonism model induced by 6-hydroxy-dopamine. The apomorphine-induced rotational behavior, characteristic of this model, and histological analysis of tyrosine hydroxylase expression were used as parameters to determine the effects of the used treatments. The obtained results obtained show that the blockade of P2X7R by BBG induced a significant decrease of apomorphine-evoked rotations and the recovery of dopaminergic neurons in the substantia nigra. However, treatments with fenofibrate and neural progenitor cells did not promote any improvement compared to animals treated with saline. In summary, we can conclude that P2X7R may be an important therapeutic target in Parkinson's disease.