Bassani Taysa Bervian, Bartolomeo Cynthia Silva, Oliveira Rafaela Brito, Ureshino Rodrigo Portes
Department of Biological Sciences, Universidade Federal de São Paulo, Diadema, Brazil.
Laboratory of Molecular and Translational Endocrinology, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.
Neuroendocrinology. 2023;113(1):14-35. doi: 10.1159/000525677. Epub 2022 Jun 27.
Neuroactive steroids can be synthetic or endogenous molecules produced by neuronal and glial cells and peripheral glands. Examples include estrogens, testosterone, progesterone and its reduced metabolites such as 5α-dihydro-progesterone and allopregnanolone. Steroids produced by neurons and glia target the nervous system and are called neurosteroids. Progesterone and analog molecules, known as progestogens, have been shown to exhibit neurotrophic, neuroprotective, antioxidant, anti-inflammatory, glial modulatory, promyelinating, and remyelinating effects in several experimental models of neurodegenerative and injury conditions. Pleiotropic mechanisms of progestogens may act synergistically to prevent neuron degeneration, astrocyte and microglial reactivity, reducing morbidity and mortality. The aim of this review is to summarize the significant findings related to the actions of progesterone and other progestogens in experimental models and epidemiological and clinical trials of some of the most prevalent and debilitating chronic neurodegenerative disorders, namely, Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and multiple sclerosis. We evaluated progestogen alterations under pathological conditions, how pathology modifies their levels, as well as the intracellular mechanisms and glial interactions underlying their neuroprotective effects. Furthermore, an analysis of the potential of natural progestogens and synthetic progestins as neuroprotective and regenerative agents, when administered as hormone replacement therapy in menopause, is also discussed.
神经活性类固醇可以是由神经元、神经胶质细胞和外周腺体产生的合成或内源性分子。例子包括雌激素、睾酮、孕酮及其还原代谢产物，如5α-二氢孕酮和别孕烯醇酮。由神经元和神经胶质产生的类固醇作用于神经系统，被称为神经甾体。孕酮及类似分子，即孕激素，已在几种神经退行性疾病和损伤状况的实验模型中显示出具有神经营养、神经保护、抗氧化、抗炎、调节神经胶质细胞、促进髓鞘形成和髓鞘再生的作用。孕激素的多效性机制可能协同作用以防止神经元变性、星形胶质细胞和小胶质细胞反应，降低发病率和死亡率。本综述的目的是总结与孕酮和其他孕激素在一些最常见且使人衰弱的慢性神经退行性疾病（即阿尔茨海默病、帕金森病、亨廷顿病、肌萎缩侧索硬化症和多发性硬化症）的实验模型以及流行病学和临床试验中的作用相关的重要发现。我们评估了病理状况下孕激素的变化、病理如何改变其水平，以及其神经保护作用背后的细胞内机制和神经胶质细胞相互作用。此外，还讨论了天然孕激素和合成孕激素在绝经后作为激素替代疗法给药时作为神经保护和再生剂的潜力。
