Pathophysiological implications of neurovascular P450 in brain disorders

•Brain P450 enzymes constitute an extra-hepatic line of drug metabolism.•P450s expressed in brain cells contribute to neurotoxicity or neuroprotection.•Neurovascular P450 enzymes could contribute to CNS drug resistances.

Over the past decades, the significance of cytochrome P450 (CYP) enzymes has expanded beyond their role as peripheral drug metabolizers in the liver and gut. CYP enzymes are also functionally active at the neurovascular interface. CYP expression is modulated by disease states, impacting cellular functions, detoxification, and reactivity to toxic stimuli and brain drug biotransformation. Unveiling the physiological and molecular complexity of brain P450 enzymes will improve our understanding of the mechanisms underlying brain drug availability, pharmacological efficacy, and neurotoxic adverse effects from pharmacotherapy targeting brain disorders.