Brain Cytochrome P450: Navigating Neurological Health and Metabolic Regulation
Human cytochrome P450 (CYP) enzymes in the brain represent a crucial frontier in neuroscience, with far-reaching implications for drug detoxification, cellular metabolism, and the progression of neurodegenerative diseases. The brain’s complex architecture, composed of interconnected cell types and r...
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MDPI AG
2025-03-01
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| Series: | Journal of Xenobiotics |
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| Online Access: | https://www.mdpi.com/2039-4713/15/2/44 |
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| author | Pradeepraj Durairaj Zixiang Leonardo Liu |
| author_facet | Pradeepraj Durairaj Zixiang Leonardo Liu |
| author_sort | Pradeepraj Durairaj |
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| description | Human cytochrome P450 (CYP) enzymes in the brain represent a crucial frontier in neuroscience, with far-reaching implications for drug detoxification, cellular metabolism, and the progression of neurodegenerative diseases. The brain’s complex architecture, composed of interconnected cell types and receptors, drives unique neuronal signaling pathways, modulates enzyme functions, and leads to distinct CYP gene expression and regulation patterns compared to the liver. Despite their relatively low levels of expression, brain CYPs exert significant influence on drug responses, neurotoxin susceptibility, behavior, and neurological disease risk. These enzymes are essential for maintaining brain homeostasis, mediating cholesterol turnover, and synthesizing and metabolizing neurochemicals, neurosteroids, and neurotransmitters. Moreover, they are key participants in oxidative stress responses, neuroprotection, and the regulation of inflammation. In addition to their roles in metabolizing psychotropic drugs, substances of abuse, and endogenous compounds, brain CYPs impact drug efficacy, safety, and resistance, underscoring their importance beyond traditional drug metabolism. Their involvement in critical physiological processes also links them to neuroprotection, with significant implications for the onset and progression of neurodegenerative diseases. Understanding the roles of cerebral CYP enzymes is vital for advancing neuroprotective strategies, personalizing treatments for brain disorders, and developing CNS-targeting therapeutics. This review explores the emerging roles of CYP enzymes, particularly those within the CYP1–3 and CYP46 families, highlighting their functional diversity and the pathological consequences of their dysregulation on neurological health. It also examines the potential of cerebral CYP-based biomarkers to improve the diagnosis and treatment of neurodegenerative disorders, offering new avenues for therapeutic innovation. |
| format | Article |
| id | doaj-art-ca2c48ae92a94eca948d81137b5303ca |
| institution | OA Journals |
| issn | 2039-4705 2039-4713 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | MDPI AG |
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| series | Journal of Xenobiotics |
| spelling | doaj-art-ca2c48ae92a94eca948d81137b5303ca2025-08-20T02:18:19ZengMDPI AGJournal of Xenobiotics2039-47052039-47132025-03-011524410.3390/jox15020044Brain Cytochrome P450: Navigating Neurological Health and Metabolic RegulationPradeepraj Durairaj0Zixiang Leonardo Liu1Department of Chemical and Biomedical Engineering, Florida State University, Tallahassee, FL 32310, USADepartment of Chemical and Biomedical Engineering, Florida State University, Tallahassee, FL 32310, USAHuman cytochrome P450 (CYP) enzymes in the brain represent a crucial frontier in neuroscience, with far-reaching implications for drug detoxification, cellular metabolism, and the progression of neurodegenerative diseases. The brain’s complex architecture, composed of interconnected cell types and receptors, drives unique neuronal signaling pathways, modulates enzyme functions, and leads to distinct CYP gene expression and regulation patterns compared to the liver. Despite their relatively low levels of expression, brain CYPs exert significant influence on drug responses, neurotoxin susceptibility, behavior, and neurological disease risk. These enzymes are essential for maintaining brain homeostasis, mediating cholesterol turnover, and synthesizing and metabolizing neurochemicals, neurosteroids, and neurotransmitters. Moreover, they are key participants in oxidative stress responses, neuroprotection, and the regulation of inflammation. In addition to their roles in metabolizing psychotropic drugs, substances of abuse, and endogenous compounds, brain CYPs impact drug efficacy, safety, and resistance, underscoring their importance beyond traditional drug metabolism. Their involvement in critical physiological processes also links them to neuroprotection, with significant implications for the onset and progression of neurodegenerative diseases. Understanding the roles of cerebral CYP enzymes is vital for advancing neuroprotective strategies, personalizing treatments for brain disorders, and developing CNS-targeting therapeutics. This review explores the emerging roles of CYP enzymes, particularly those within the CYP1–3 and CYP46 families, highlighting their functional diversity and the pathological consequences of their dysregulation on neurological health. It also examines the potential of cerebral CYP-based biomarkers to improve the diagnosis and treatment of neurodegenerative disorders, offering new avenues for therapeutic innovation.https://www.mdpi.com/2039-4713/15/2/44cytochrome P450xenobiotic-metabolizing enzymesbrainneurological healthneurochemistryneurodegeneration |
| spellingShingle | Pradeepraj Durairaj Zixiang Leonardo Liu Brain Cytochrome P450: Navigating Neurological Health and Metabolic Regulation Journal of Xenobiotics cytochrome P450 xenobiotic-metabolizing enzymes brain neurological health neurochemistry neurodegeneration |
| title | Brain Cytochrome P450: Navigating Neurological Health and Metabolic Regulation |
| title_full | Brain Cytochrome P450: Navigating Neurological Health and Metabolic Regulation |
| title_fullStr | Brain Cytochrome P450: Navigating Neurological Health and Metabolic Regulation |
| title_full_unstemmed | Brain Cytochrome P450: Navigating Neurological Health and Metabolic Regulation |
| title_short | Brain Cytochrome P450: Navigating Neurological Health and Metabolic Regulation |
| title_sort | brain cytochrome p450 navigating neurological health and metabolic regulation |
| topic | cytochrome P450 xenobiotic-metabolizing enzymes brain neurological health neurochemistry neurodegeneration |
| url | https://www.mdpi.com/2039-4713/15/2/44 |
| work_keys_str_mv | AT pradeeprajdurairaj braincytochromep450navigatingneurologicalhealthandmetabolicregulation AT zixiangleonardoliu braincytochromep450navigatingneurologicalhealthandmetabolicregulation |