Neurosteroidogenic enzymes: CYP11A1 in the central nervous system |
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| Affiliation: | 1. Department of Biomedical Sciences, College of Medicine, Korea University, Seoul 02841, Korea;2. Department of Physiology, College of Medicine, Korea University, Seoul 02841, Korea;1. School of Chemistry and Biochemistry, The University of Western Australia, Crawley, WA, Australia;2. Department of Pathology and Laboratory Medicine, Center for Cancer Research, University of Tennessee Health Science Center, Memphis, TN, USA;3. Department of Medicine, Division of Rheumatology and Connective Tissue Diseases, University of Tennessee Health Science Center, Memphis, TN, USA;4. Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN, USA;5. Department of Pharmaceutical Sciences, School of Pharmacy, South College, Knoxville, TN, USA;1. Institute of Biochemistry, Saarland University, 66123 Saarbrücken, Germany;2. Institute of Pharmaceutical Biology, Saarland University, 66123 Saarbrücken, Germany;1. Department of Pathology and Laboratory Medicine, Memphis, TN, USA;2. Division of Rheumatology and Connective Tissue Diseases of the Department of Medicine, Memphis, TN, USA;3. Department of Pharmaceutical Sciences, Memphis, TN, USA;4. Department of Paediatrics, Memphis, TN, USA;5. Center for Adult Cancer Research, University of Tennessee HSC, Memphis, TN, USA;6. Veteran Administration, Memphis, TN, USA;7. School of Chemistry and Biochemistry, The University of Western Australia, Crawley, WA, Australia |
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| Abstract: | Neurosteroids, steroid hormones synthesized locally in the nervous system, have important neuromodulatory and neuroprotective effects in the central nervous system. Progress in neurosteroid research has led to the successful translation of allopregnanolone into an approved therapy for postpartum depression. However, there is insufficient evidence to support the assumption that steroidogenesis is exactly the same between the nervous system and the periphery. This review focuses on CYP11A1, the only enzyme currently known to catalyze the first reaction in steroidogenesis to produce pregnenolone, the precursor to all other steroids. Although CYP11A1 mRNA has been found in brain of many mammals, the presence of CYP11A1 protein has been difficult to detect, particularly in humans. Here, we highlight the discrepancies in the current evidence for CYP11A1 in the central nervous system and propose new directions for understanding neurosteroidogenesis, which will be crucial for developing neurosteroid-based therapies for the future. |
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| Keywords: | Neurosteroids CYP11A1 Cytochrome P450 Steroidogenesis Pregnenolone Central nervous system Brain Spinal cord Retina |
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