CYP2D6, Its Genetic Polymorphism, and the Brain

Abstract

Cytochrome P450 system comprises of several families of non-specific monooxygenases that catalyze Phase-I biotransformation reactions of an extensive list of drugs. The genes encoding for these Cytochrome P450 (CYP) enzymes are highly polymorphic. Further, these enzymes are susceptible to inhibition or induction by various drugs. So far, these enzymes have been extensively studied in context to drug-drug interactions and drug-gene interactions. However, their role in different organs other than liver and intestines during health and disease remain largely unknown. Among these CYP enzymes, CYP2D6 represents a highly polymorphic isozyme that has low content in the liver compared to other isozymes, yet metabolizes a significant proportion of the clinically used drugs. This mini review explores the role of CYP2D6 in the brain during health and disease. CYP2D6 is expressed in different regions of the brain and also, its expression varies among different brain cells. CYP2D6 and its genetic polymorphism have important impact on the normal brain functions ranging from brain metabolism, cerebral perfusion to cognition and behavior. CYP2D6 and its genotypes are also associated with the risk of Parkinson’s disease, Schizophrenia, and depression. Since, CYP2D6 activity can be modulatable, therefore, it represents a potential modulatable therapeutic target that can be used to treat various neuropsychiatric, neurodegenerative and cerebrovascular diseases.