Novas perspectivas para tratamento da doença de Parkinson

Abstract

The main pathological features of Parkinson's disease (PD) include large loss of dopaminergic neurons in the substance nigra pars compact and -synuclein deposits in the remaining neurons. PD is characterized by typical motor and non-motor symptoms. Until now, there is no neuroprotective treatment able to retard the progression of the disease and bring greater benefits on PD symptoms. Important advances have been made regarding the pathways leading to cell dysfunction and death in PD. Some of the pathways that have been studied include mitochondrial dysfunction, oxidative stress, calcium regulation, inflammation and protein aggregation. Interaction with calcium channels may represent a suitable therapeutic intervention target for delaying PD progression. Mitochondrial dysfunction and increased oxidative stress are also involved in the pathogenesis of PD, being both potential targets for intervention. Incorrect folding of the protein -sinuclein leads to the formation of protein aggregates toxic to the cells. Therefore, strategies that improve the elimination of misfolded proteins would be good alternatives for PD treatment. Agonists of 5-HT1A receptor did improve the motor symptoms of PD, dyskinesia induced by levodopa, cognitive deficiencies and vomiting. The excitotoxicity mediated by glutamate can contribute to the mechanisms that trigger the neurodegenerative process in the substantia nigra pars compacta. Then, the development of new molecules or pharmacological strategies to act on glutamate receptors also configures a possible target. The regulation of apoptosis through interactions members of the Bcl-2 family and caspase cascades may also be an alternative for interventional treatment of PD.