Melcangi Roberto C, Cavarretta Ilaria T R, Ballabio Marinella, Leonelli Emanuela, Schenone Angelo, Azcoitia Inigo, Miguel Garcia-Segura Luis, Magnaghi Valerio
Department of Endocrinology, University of Milan, Italy.
Brain Res Brain Res Rev. 2005 Apr;48(2):328-38. doi: 10.1016/j.brainresrev.2004.12.021. Epub 2005 Jan 28.
Peripheral nervous system possesses both classical and non-classical steroid receptors and consequently may represent a target for the action of neuroactive steroids. The present review summarizes the state of art of this intriguing field of research reporting data which indicate that neuroactive steroids, like for instance progesterone, dihydroprogesterone, tetrahydroprogesterone, dihydrotestosterone and 3alpha-diol, stimulate the expression of two important proteins of the myelin of peripheral nerves, the glycoprotein P0 (P0) and the peripheral myelin protein 22 (PMP22). Interestingly, the mechanisms by which neuroactive steroids exert their effects involve classical steroid receptors, like for instance progesterone and androgen receptors, in case of P0 and non-classical steroid receptors, like GABA(A) receptor, in case of PMP22. Moreover, neuroactive steroids not only control the expression of these specific myelin proteins, but also influence the morphology of myelin sheaths and axons suggesting that these molecules may represent an interesting new therapeutic approach to maintain peripheral nerve integrity during neurodegenerative events.
外周神经系统同时拥有经典和非经典类固醇受体,因此可能是神经活性类固醇作用的靶点。本综述总结了这一有趣研究领域的现状,报告的数据表明,神经活性类固醇,例如孕酮、二氢孕酮、四氢孕酮、二氢睾酮和3α -二醇,可刺激外周神经髓鞘的两种重要蛋白质,即糖蛋白P0(P0)和外周髓鞘蛋白22(PMP22)的表达。有趣的是,神经活性类固醇发挥作用的机制在P0的情况下涉及经典类固醇受体,例如孕酮和雄激素受体,而在PMP22的情况下涉及非经典类固醇受体,例如GABA(A)受体。此外,神经活性类固醇不仅控制这些特定髓鞘蛋白的表达,还影响髓鞘和轴突的形态,这表明这些分子可能代表一种有趣的新治疗方法,用于在神经退行性病变期间维持外周神经的完整性。