Pathophysiological implications of neurovascular P450 in brain disorders.
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.
Cerebrovascular Research, Cleveland Clinic Lerner Research Institute, Cleveland, OH, USA; Department of Biomedical Engineering, Cleveland Clinic Lerner Research Institute, Cleveland, OH, USA; Department of Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH, USA. Electronic address: GHOSHC@ccf.org.
Chaitali
C
Ghosh
Cerebrovascular Research, Cleveland Clinic Lerner Research Institute, Cleveland, OH, USA; Department of Biomedical Engineering, Cleveland Clinic Lerner Research Institute, Cleveland, OH, USA.
Mohammed
M
Hossain
The Ohio State University, Columbus, OH, USA.
Jesal
J
Solanki
The Ohio State University, Columbus, OH, USA.
Aaron
A
Dadas
Cerebrovascular Mechanisms of Brain Disorders, Department of Neuroscience, Institute of Functional Genomics (CNRS/INSERM), Montpellier, France.
Nicola
N
Marchi
Flocel Inc. and Case Western Reserve University, Cleveland, OH, USA.
Damir
D
Janigro
D000818:Animals; D001711:Biotransformation; D001921:Brain / Q000378:metabolism*; D001927:Brain Diseases / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D055808:Drug Discovery; D004347:Drug Interactions; D006801:Humans
D003577:Cytochrome P-450 Enzyme System