The role of cytochrome P450 and gut microbiome in drug metabolism: Insights into Parkinson disease treatment.

Parkinson disease (PD) is a complex neurodegenerative condition marked by progressive motor and nonmotor symptoms. Cytochrome P450 (P450) enzymes, notably those from the CYP1 and CYP2 families, are increasingly recognized as significant factors in the development of PD. This review examines the role of P450 enzymes in PD, covering genetic variations, copy number variations, and single nucleotide polymorphisms linked to PD pathogenicity. It also explores the regulatory mechanisms controlling P450 expression in PD and the influence of the gut microbiome and metabolites on P450 activity. Additionally, the review discusses how P450 enzymes metabolically activate drugs used to treat PD and investigates the intricate relationship between P450s and mitochondrial dysfunction. Finally, it underscores the therapeutic potential of targeting P450 enzymes for PD treatment. Understanding the diverse roles of P450 enzymes in PD may lead to innovative treatment approaches and personalized interventions for this challenging neurological disorder. SIGNIFICANCE STATEMENT: Cytochrome P450 (P450) enzymes significantly influence Parkinson disease (PD) development through their roles in drug metabolism and detoxification. Single nucleotide polymorphisms in P450 genes can alter enzyme activity, affecting PD susceptibility and progression. Gut microbiota modulates P450 function, impacting detoxification of PD-related toxins and influencing gut and blood-brain barrier integrity. Additionally, P450-mitochondrial interactions contribute to energy deficits and oxidative stress, exacerbating neurodegeneration in PD. Understanding these pathways may uncover novel therapeutic targets and personalized treatment strategies.