Cytochrome P450 2D6 and Parkinson's Disease: Polymorphism, Metabolic Role, Risk and Protection.

Cytochrome P450 2D6 and Parkinson's Disease: Polymorphism, Metabolic Role, Risk and Protection. Neurochem Res. 2017 Sep 04;: Authors: Ur Rasheed MS, Mishra AK, Singh MP Abstract Cytochrome P450 (CYP) 2D6 is one of the most highly active, oxidative and polymorphic enzymes known to metabolize Parkinsonian toxins and clinically established anti-Parkinson's disease (PD) drugs. Albeit CYP2D6 gene is not present in rodents, its orthologs perform almost the similar function with imprecise substrate and inhibitor specificity. CYP2D6 expression and catalytic activity are found to be regulated at every stage of the central dogma except replication as well as at the epigenetic level. CYP2D6 gene codes for a set of alternate splice variants that give rise to a range of enzymes possessing variable catalytic activity. Case-control studies, meta-analysis and systemic reviews covering CYP2D6 polymorphism and PD risk have demonstrated that poor metabolizer phenotype possesses a considerable genetic susceptibility. Besides, ultra-rapid metabolizer offers protection against the risk in some populations while lack of positive or inverse association is also reported in other inhabitants. CYP2D6 polymorphisms resulting into deviant protein products with differing catalytic activity could lead to inter-individual variations, which could be explained to certain extent on the basis of sample size, life style factors, food habits, ethnicity and tools used for...
Source: Neurochemical Research - Category: Neuroscience Authors: Tags: Neurochem Res Source Type: research