Nuclear hormone receptors in demyelinating diseases.
Nuclear hormone receptors in demyelinating diseases.
复制标题
脱髓鞘疾病中的核激素受体。
DOI：
10.1111/jne.13171
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发表时间：
2022-07
影响因子：
3.2
通讯作者：
Hu, Jian
中科院分区：
文献类型：
--
作者：
Veloz, Rocio I. Zorrilla;McKenzie, Takese;Palacios, Bridgitte E.;Hu, Jian
脱髓鞘由髓鞘的病理性损失引起，并且是许多神经退行性疾病的标志。尽管脱髓鞘疾病普遍存在，但没有预防髓鞘损失或促进髓鞘再生的疾病修饰疗法。这篇综述的目的是总结该领域的研究，突出了核激素受体在促进和维持髓鞘形成的重要性，以及核激素受体作为脱髓鞘疾病潜在治疗靶点的相关性。这些核激素受体包括雌激素受体、孕激素受体、雄激素受体、维生素D受体、甲状腺激素受体、过氧化物酶体增殖物激活受体、肝X受体和类维生素A X受体。在成熟的脱髓鞘动物模型中进行的临床前研究表明，这些核激素受体通过促进少突胶质细胞成熟和发育在髓鞘形成中发挥着重要作用。在脱髓鞘的小鼠模型中，核激素受体通过其配体的活化也促进髓鞘蛋白和脂质的合成。有有限的临床研究，重点是如何激活这些核激素受体可以减轻疾病，如多发性硬化症（MS）患者的脱髓鞘。然而，已完成的临床试验报告了用这些核激素受体中的一些的配体治疗的MS患者的改善的临床结果。总之，临床和临床前研究的积极结果表明，核激素受体是对抗脱髓鞘的有希望的治疗靶点。
Demyelination results from the pathological loss of myelin and is a hallmark of many neurodegenerative diseases. Despite the prevalence of demyelinating diseases, there are no disease modifying therapies that prevent the loss of myelin or promote remyelination. This review aims to summarize studies in the field that highlight the importance of nuclear hormone receptors in the promotion and maintenance of myelination and the relevance of nuclear hormone receptors as potential therapeutic targets for demyelinating diseases. These nuclear hormone receptors include the estrogen receptor, progesterone receptor, androgen receptor, vitamin D receptor, thyroid hormone receptor, peroxisome proliferator-activated receptor, liver X receptor, and retinoid X receptor. Pre-clinical studies in well-established animal models of demyelination have shown a prominent role of these nuclear hormone receptors in myelination through their promotion of oligodendrocyte maturation and development. The activation of the nuclear hormone receptors by their ligands also promotes the synthesis of myelin proteins and lipids in mouse models of demyelination. There are limited clinical studies that focus on how the activation of these nuclear hormone receptors could alleviate demyelination in patients with diseases such as Multiple sclerosis (MS). However, the completed clinical trials have reported improved clinical outcome in MS patients treated with the ligands of some of these nuclear hormone receptors. Together, the positive results from both clinical and pre-clinical studies point to nuclear hormone receptors as promising therapeutic targets to counter demyelination.
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