Pathophysiological implications of neurovascular P450 in brain disorders.

Pathophysiological implications of neurovascular P450 in brain disorders.
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DOI:
10.1016/j.drudis.2016.06.004
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发表时间:
2016-10
影响因子:
7.4
通讯作者:
Janigro, Damir
Janigro, Damir
中科院分区:
医学2区
文献类型:
--
作者:
Ghosh, Chaitali;Hossain, Mohammed;Solanki, Jesal;Dadas, Aaron;Marchi, Nicola;Janigro, Damir

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在过去的几十年里,细胞色素 P450 (CYP) 酶的重要性已经超出了其作为肝脏和肠道外周药物代谢物的作用。 CYP 酶在神经血管界面也具有功能活性。 CYP 表达受疾病状态调节,影响细胞功能、解毒、对有毒刺激的反应性和脑药物生物转化。揭示大脑 P450 酶的生理和分子复杂性将提高我们对大脑药物可用性、药理功效以及针对大脑疾病的药物治疗的神经毒性副作用的机制的理解。
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.
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