A PILOT STUDY TO EXAMINE THE ROLE OF DRUG METABOLIZING ENZYMES IN PARKINSON'S DESEASE

Abstract

1. ABSTRACT Parkinson’s disease is a progressive neurodegenerative disorder which is characterized by loss of dopaminergic neurons in the brain. It affects more than 1% of the world’s population. Levodopa, a precursor of dopamine (neurotransmitter responsible for movements) is the drug of choice for treatment of Parkinson’s disease. Levodopa is metabolized to dopamine by Dopa decarboxylase enzyme. In addition, dopamine is metabolized to other non-functional forms by catechol-o-methyl transferase and monoamine oxidase enzymes. Hence, these three enzymes appear to be important for bioavailability of levodopa. In this study, we have examined the role of drug metabolizing enzymes in Parkinson’s disease. In addition, pathogenesis of Parkinson’s disease has been shown to be associated with protein aggregation. We also examined the role of two important molecular chaperones (Hsp70 and GrP78) implicated in Parkinson’s disease. The expression levels of these enzymes and chaperones in patients were compared to heathy controls by real time PCR. Though the sample size (six patients and six healthy controls) was small, our results indicate that COMT and MAOB downregulated. However, no conclusive change was observed in molecular chaperones. The study needs to be extended to larger sample set to define a correlation of these enzymes with drug response in Parkinson’s disease.