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神经活性甾体和帕金森病:人体和动物研究综述。

Neuroactive steroids and Parkinson's disease: Review of human and animal studies.

机构信息

Centre de Recherche du CHU de Québec-Université Laval, Axe Neurosciences, 2705, Boulevard Laurier, Québec G1V4G2, Canada.

Centre de Recherche du CHU de Québec-Université Laval, Axe Neurosciences, 2705, Boulevard Laurier, Québec G1V4G2, Canada; Faculté de pharmacie, Pavillon Ferdinand-Vandry, 1050, avenue de la Médecine, Université Laval, Québec G1V 0A6, Canada.

出版信息

Neurosci Biobehav Rev. 2024 Jan;156:105479. doi: 10.1016/j.neubiorev.2023.105479. Epub 2023 Nov 23.

Abstract

The greater prevalence and incidence of Parkinson's disease (PD) in men suggest a beneficial effect of sex hormones. Neuroactive steroids have neuroprotective activities thus offering interesting option for disease-modifying therapy for PD. Neuroactive steroids are also neuromodulators of neurotransmitter systems and may thus help to control PD symptoms and side effect of dopamine medication. Here, we review the effect on sex hormones (estrogen, androgen, progesterone and its metabolites) as well as androstenediol, pregnenolone and dehydroepiandrosterone) in human studies and in animal models of PD. The effect of neuroactive steroids is reviewed by considering sex and hormonal status to help identify specifically for women and men with PD what might be a preventive approach or a symptomatic treatment. PD is a complex disease and the pathogenesis likely involves multiple cellular processes. Thus it might be useful to target different cellular mechanisms that contribute to neuronal loss and neuroactive steroids provide therapeutics options as they have multiple mechanisms of action.

摘要

帕金森病(PD)在男性中的患病率和发病率更高,这表明性激素可能具有有益作用。神经活性甾体具有神经保护活性,因此为 PD 的疾病修饰治疗提供了有趣的选择。神经活性甾体也是神经递质系统的神经调节剂,因此可能有助于控制 PD 症状和多巴胺药物的副作用。在这里,我们回顾了人类研究和 PD 动物模型中性激素(雌激素、雄激素、孕激素及其代谢物)以及雄烯二酮、孕烯醇酮和脱氢表雄酮)的作用。通过考虑性别和激素状态来审查神经活性甾体的作用,以帮助确定 PD 女性和男性的具体预防方法或症状治疗方法。PD 是一种复杂的疾病,其发病机制可能涉及多种细胞过程。因此,针对导致神经元丧失的不同细胞机制可能会很有用,而神经活性甾体则提供了治疗选择,因为它们具有多种作用机制。

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