P450 ENZYMES AND PARKINSONS-DISEASE - THE STORY SO FAR

Environmental or endogenous toxins may cause nigral cell death in Park inson's disease (PD) as a result of genetic susceptibility conferred b y altered expression of P450 enzymes. Attention over the last 10 years has focused on CYP2D6 polymorphisms and susceptibility to PD. This re view summarizes reports arising from both phenotypic and genotypic stu dies involving CYP2D6 and PD. Phenotypic studies have failed to suppor t a link between CYP2D6 and PD, The more powerful genetic studies init ially indicated a link between CYP2D6B mutations and PD, but critical analysis of the literature and recent studies emerging from Independen t laboratories fail to confirm this. Mutations in CYP2D6B are also not implicated in familial PD. As yet, there is no conclusive evidence to suggest that CYP2D6 polymorphisms confer susceptibility to PD. Whethe r polymorphisms in other P450s (for example, CYP1A1 and CYP2E1) are im plicated in PD remains to be established.