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Interactions of Aromatase and Seladin-1: A Neurosteroidogenic and Gender Perspective.
Translational Neuroscience ( IF 2.1 ) Pub Date : 2019-11-19 , DOI: 10.1515/tnsci-2019-0043
Pelin Kelicen-Ugur 1 , Mehtap Cincioğlu-Palabıyık 2 , Hande Çelik 1 , Hande Karahan 3, 4
Affiliation  

Aromatase and seladin-1 are enzymes that have major roles in estrogen synthesis and are important in both brain physiology and pathology. Aromatase is the key enzyme that catalyzes estrogen biosynthesis from androgen precursors and regulates the brain's neurosteroidogenic activity. Seladin-1 is the enzyme that catalyzes the last step in the biosynthesis of cholesterol, the precursor of all hormones, from desmosterol. Studies indicated that seladin-1 is a downstream mediator of the neuroprotective activity of estrogen. Recently, we also showed that there is an interaction between aromatase and seladin-1 in the brain. Therefore, the expression of local brain aromatase and seladin-1 is important, as they produce neuroactive steroids in the brain for the protection of neuronal damage. Increasing steroid biosynthesis specifically in the central nervous system (CNS) without affecting peripheral hormone levels may be possible by manipulating brain-specific promoters of steroidogenic enzymes. This review emphasizes that local estrogen, rather than plasma estrogen, may be responsible for estrogens' protective effects in the brain. Therefore, the roles of aromatase and seladin-1 and their interactions in neurodegenerative events such as Alzheimer's disease (AD), ischemia/reperfusion injury (stroke), and epilepsy are also discussed in this review.

中文翻译:

芳香酶和Seladin-1的相互作用:神经甾体生成和性别视角。

Aromatase和seladin-1是在雌激素合成中起主要作用的酶,在脑生理和病理学中均很重要。芳香酶是催化雄激素前体合成雌激素并调节大脑神经甾体生成活性的关键酶。Seladin-1是一种酶,可催化去氢甾醇中所有激素的前体胆固醇的生物合成中的最后一步。研究表明,seladin-1是雌激素神经保护活性的下游介质。最近,我们还表明,大脑中的芳香化酶和seladin-1之间存在相互作用。因此,局部大脑芳香酶和seladin-1的表达很重要,因为它们在大脑中产生神经活性类固醇来保护神经元损伤。通过操纵类固醇生成酶的大脑特异性启动子,可以在中枢神经系统(CNS)中增加类固醇的生物合成,而又不影响周围激素水平。该评论强调,局部雌激素而不是血浆雌激素可能是导致雌激素对大脑的保护作用的原因。因此,本篇综述还讨论了芳香化酶和seladin-1的作用及其在神经退行性事件(如阿尔茨海默氏病(AD),局部缺血/再灌注损伤(中风)和癫痫病)中的相互作用。对大脑的保护作用。因此,本篇综述还讨论了芳香化酶和seladin-1的作用及其在神经退行性事件(如阿尔茨海默氏病(AD),局部缺血/再灌注损伤(中风)和癫痫病)中的相互作用。对大脑的保护作用。因此,本篇综述还讨论了芳香化酶和seladin-1的作用及其在神经退行性事件(如阿尔茨海默氏病(AD),局部缺血/再灌注损伤(中风)和癫痫病)中的相互作用。
更新日期:2019-11-01
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