Neurodegenerative diseases are characterized by a progressive loss of neurons that leads to a broad range of disabilities, including severe cognitive decline and motor impairment, for which there are no effective therapies. Several lines of evidence support a putative therapeutic role of nuclear receptors (NRs) in these types of disorders. NRs are ligand-activated transcription factors that regulate the expression of a wide range of genes linked to metabolism and inflammation. Although the activation of NRs in animal models of neurodegenerative disease exhibits promising results, the translation of this strategy to clinical practice has been unsuccessful. In this review we discuss the role of NRs in neurodegenerative diseases in light of preclinical and clinical studies, as well as new findings derived from the analysis of transcriptomic databases from humans and animal models. We discuss the failure in the translation of NR-based therapeutic approaches and consider alternative and novel research avenues in the development of effective therapies for neurodegenerative diseases.

中文翻译：

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核受体作为神经退行性疾病的治疗靶标：翻译中遗失。

神经退行性疾病的特征是神经元的逐渐丧失，导致广泛的残疾，包括严重的认知能力下降和运动障碍，目前尚无有效的治疗方法。有几条证据支持在这些类型的疾病中核受体（NRs）的假定治疗作用。NR是配体激活的转录因子，可调节与代谢和炎症相关的多种基因的表达。尽管在神经退行性疾病的动物模型中激活NRs表现出令人鼓舞的结果，但这种策略在临床实践中的应用仍未成功。在这篇综述中，我们将根据临床前和临床研究来探讨NRs在神经退行性疾病中的作用，以及从人类和动物模型的转录组数据库分析得出的新发现。我们讨论基于NR的治疗方法的翻译失败，并在神经退行性疾病的有效疗法的发展中考虑替代和新颖的研究途径。