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Advisor(s)
Abstract(s)
A doença de Parkinson é um transtorno crónico e progressivo do movimento. Segundo dados da Associação Europeia de Doença de Parkinson, esta doença afeta mais de 1,2 milhões de pessoas em toda a Europa e está associada a um custo anual estimado de 13,9 mil milhões de euros.
O maior fator de risco para a Doença de Parkinson é a idade. A idade média de início é de 60 anos, embora mais de uma em cada dez pessoas sejam diagnosticadas antes dos 50 anos. Esta patologia é predominantemente caracterizada por sintomas motores, mas também é acompanhada por uma ampla gama de sintomas não-motores que incluem disfunções do sistema nervoso autónomo e distúrbios comportamentais.
Atualmente, não há cura ou tratamento capaz de retardar ou interromper a progressão da doença e, embora na fase inicial o tratamento da Doença de Parkinson traga um alívio sintomático marcado, ao longo do tempo os efeitos colaterais como discinesia, comportamento impulsivo e compulsivo, alucinações e delírios podem surgir.
A Doença de Parkinson é uma doença idiopática que parece resultar de interações ambientais com fatores de predisposição genética. Até à data, os eventos iniciais subjacentes aos processos neurodegenerativos na doença não são bem compreendidos, contudo a desregulação do stress oxidativo é aceite como um dos processos precipitantes e/ou potenciadores da morte neuronal que ocorre nesta patologia. A presença de dopamina, os elevados níveis de ferro na substantia nigra ou a elevada suscetibilidade dos neurónios dopaminérgicos aos processos inflamatórios são exemplos de fatores geradores de stress oxidativo. Por outro lado, mutações associadas à doença em genes que codificam proteínas mitocondriais ou proteínas reconhecidas como antioxidantes são também possíveis contribuidores do stress oxidativo.
Vários marcadores oxidativos, quer do tecido cerebral, quer em tecidos periféricos de doentes de DP comprovam o estado pró-oxidativo na doença. Alguns estudos sugerem ainda que este estado oxidativo pode ser favorecido pelas terapias que visam repor a transmissão dopaminérgica como a levodopa ou os agonistas dopaminérgicos.
As evidências que mostram a relação entre elevados níveis de stress oxidativo e a Doença de Parkinson levaram vários grupos de investigação a avaliar o impacto de estratégias baseadas no uso de antioxidantes em controlar os marcadores oxidativos e em travar os sintomas da doença. A Coenzima Q10, Pioglitazona ou os Inibidores da mieloperoxidase são exemplos de compostos com atividade antioxidantes estudados neste âmbito.
O presente trabalho teve como objetivo rever a informação existente sobre a relação entre o stress oxidativo e a Doença de Parkinson e analisar os dados existentes sobre o potencial dos antioxidantes como possível estratégia terapêutica nesta patologia.
Parkinson's disease is a chronic and progressive movement disorder. According to data from the European Parkinson's Disease Association, this disease affects more than 1.2 million people across Europe and is associated with an estimated annual cost of 13.9 billion euros. The biggest risk factor for Parkinson's is age. The average age of onset is 60 years, although more than one in ten people are diagnosed before the age of 50. This pathology is predominantly characterized by motor symptoms but is also accompanied by a wide range of non-motor symptoms including autonomic nervous system dysfunction and behavioral disorders. There is currently no cure or treatment capable of delaying or disrupting the disease progression. Although early treatment of Parkinson's disease brings substantial symptomatic relief, side effects such as dyskinesia, impulsive and compulsive behavior, hallucinations and delusions may arise. Parkinson's disease is an idiopathic disease that seems to result from environmental interactions with genetic predisposition factors. To date, the initial events underlying the neurodegenerative processes in the disease are not well understood, however, the deregulation of oxidative stress is accepted as one of the precipitating processes and/or enhancers of neuronal death that occurs in this pathology. The presence of dopamine, elevated iron levels in the substantia nigra or the high susceptibility of dopaminergic neurons to inflammatory processes are examples of factors that generate oxidative stress. On the other hand, mutations associated with Parkinson’s in genes encoding mitochondrial proteins or proteins recognized as antioxidants are also possible contributors of oxidative stress. Several oxidative markers, both in brain and peripheral tissues of Parkinson’s patients, confirm the pro-oxidative state in the disease. Some studies also suggest that this oxidative state may be further enhanced by therapies aimed at restoring dopaminergic transmission such as levodopa or dopaminergic agonists. Evidence showing the relationship between elevated levels of oxidative stress and Parkinson’s Disease has led several research groups to evaluate the impact of strategies based on the use of antioxidants in controlling oxidative markers and stopping the progression of symptoms of the disease. Q10 Coenzyme, Pioglitazone or myeloperoxidase inhibitors are examples of antioxidant compounds studied herein. The objective of the present study was to review the existing information on the relationship between oxidative stress and Parkinson’s Disease and to analyze the existing data on the potential of antioxidants as a possible therapeutic strategy in this pathology.
Parkinson's disease is a chronic and progressive movement disorder. According to data from the European Parkinson's Disease Association, this disease affects more than 1.2 million people across Europe and is associated with an estimated annual cost of 13.9 billion euros. The biggest risk factor for Parkinson's is age. The average age of onset is 60 years, although more than one in ten people are diagnosed before the age of 50. This pathology is predominantly characterized by motor symptoms but is also accompanied by a wide range of non-motor symptoms including autonomic nervous system dysfunction and behavioral disorders. There is currently no cure or treatment capable of delaying or disrupting the disease progression. Although early treatment of Parkinson's disease brings substantial symptomatic relief, side effects such as dyskinesia, impulsive and compulsive behavior, hallucinations and delusions may arise. Parkinson's disease is an idiopathic disease that seems to result from environmental interactions with genetic predisposition factors. To date, the initial events underlying the neurodegenerative processes in the disease are not well understood, however, the deregulation of oxidative stress is accepted as one of the precipitating processes and/or enhancers of neuronal death that occurs in this pathology. The presence of dopamine, elevated iron levels in the substantia nigra or the high susceptibility of dopaminergic neurons to inflammatory processes are examples of factors that generate oxidative stress. On the other hand, mutations associated with Parkinson’s in genes encoding mitochondrial proteins or proteins recognized as antioxidants are also possible contributors of oxidative stress. Several oxidative markers, both in brain and peripheral tissues of Parkinson’s patients, confirm the pro-oxidative state in the disease. Some studies also suggest that this oxidative state may be further enhanced by therapies aimed at restoring dopaminergic transmission such as levodopa or dopaminergic agonists. Evidence showing the relationship between elevated levels of oxidative stress and Parkinson’s Disease has led several research groups to evaluate the impact of strategies based on the use of antioxidants in controlling oxidative markers and stopping the progression of symptoms of the disease. Q10 Coenzyme, Pioglitazone or myeloperoxidase inhibitors are examples of antioxidant compounds studied herein. The objective of the present study was to review the existing information on the relationship between oxidative stress and Parkinson’s Disease and to analyze the existing data on the potential of antioxidants as a possible therapeutic strategy in this pathology.
Description
Keywords
Antioxidantes Doença de Parkinson L-Dopa Radicais Livres Stress Oxidativo