a Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas , Universidad Nacional Autónoma de México , Ciudad de México, México.
Drug Metab Rev. 2018 May;50(2):95-108. doi: 10.1080/03602532.2018.1439502. Epub 2018 Feb 16.
Cytochromes P450 (CYPs) constitute a family of enzymes that can be found in the endoplasmic reticulum (ER), mitochondria or the cell surface of the cells. CYPs are characterized by carrying out the oxidation of organic compounds and they are mainly recognized as mediators of the biotransformation of xenobiotics to polar hydrophilic metabolites that can be eliminated from the organism. However, these enzymes play a key role in many other physiological processes, being involved in diverse indispensable metabolic pathways since they metabolize many endogenous substrates. Various CYP isoforms are expressed in the brain, and it is believed that this could be in part due to the particular function of brain CYPs. In the brain, CYPs are involved in the cholesterol turnover, the biosynthesis of dopamine, serotonin, morphine, hormones, and protective lipid mediators (epoxyeicosatrienoic acids), in addition to their already recognized role in xenobiotics detoxification and psychotropic drug metabolism. Increasing evidence suggests that this group of enzymes is fundamental for the normal functioning and maintenance of brain homeostasis. This review is focused on highlighting the importance of CYP-mediated endogenous metabolism in the central nervous system (CNS) and its relationship with recent findings regarding CYP involvement in neurodegenerative diseases. Some therapeutic approaches focused on CYP regulation are also discussed.
细胞色素 P450（CYPs）是一组存在于内质网（ER）、线粒体或细胞表面的酶。CYPs 的特征是进行有机化合物的氧化，它们主要被认为是将外源物质生物转化为极性亲水代谢物的生物转化的介质，这些代谢物可以从生物体中排出。然而，这些酶在许多其他生理过程中起着关键作用，参与了许多必不可少的代谢途径，因为它们代谢许多内源性底物。各种 CYP 同工酶在大脑中表达，人们认为这可能部分归因于大脑 CYPs 的特殊功能。在大脑中，CYPs 参与胆固醇周转、多巴胺、血清素、吗啡、激素和保护性脂质介质（环氧二十碳三烯酸）的生物合成，除了它们在外源物质解毒和精神药物代谢中的已有作用。越来越多的证据表明，这组酶对大脑的正常功能和维持脑内环境稳态至关重要。本综述重点强调了 CYP 介导的内源性代谢在中枢神经系统（CNS）中的重要性及其与 CYP 参与神经退行性疾病的最新发现的关系。还讨论了一些专注于 CYP 调节的治疗方法。
