Nuclear Receptors as Therapeutic Targets for Neurodegenerative Diseases: Lost in Translation.
Nuclear Receptors as Therapeutic Targets for Neurodegenerative Diseases: Lost in Translation.
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DOI：
10.1146/annurev-pharmtox-010818-021807
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发表时间：
2019-01-06
影响因子：
12.5
通讯作者：
Landreth GE
中科院分区：
文献类型：
--
作者：
Moutinho M;Codocedo JF;Puntambekar SS;Landreth GE
神经退行性疾病的特征在于神经元的进行性损失，其导致广泛的残疾，包括严重的认知下降和运动障碍，对此没有有效的疗法。一些证据支持核受体（NR）在这些类型的疾病中的假定治疗作用。NR是配体激活的转录因子，调节与代谢和炎症相关的广泛基因的表达。虽然在神经退行性疾病的动物模型中激活NR显示出有希望的结果，但将该策略转化为临床实践并不成功。在这篇综述中，我们讨论了NR在神经退行性疾病中的作用，根据临床前和临床研究，以及来自人类和动物模型转录组数据库分析的新发现。我们讨论了翻译NR为基础的治疗方法的失败，并考虑替代和新的研究途径，在神经退行性疾病的有效疗法的发展。
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.
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DOI：
10.3233/jhd-150181
发表时间：
2016
期刊：
Journal of Huntington's disease
影响因子：
--
作者：
Chen JY;Tran C;Hwang L;Deng G;Jung ME;Faull KF;Levine MS;Cepeda C
通讯作者：
Cepeda C
影响因子：
5.3
作者：
Bonato, Jessica Mendes;Bassani, Taysa Bervian;Weffort de Oliveira, Rubia Maria
通讯作者：
Weffort de Oliveira, Rubia Maria
DOI：
10.1097/nen.0b013e3181df20e1
发表时间：
2010-06-01
影响因子：
3.2
作者：
Bigini, Paolo;Steffensen, Knut R.;Gustafsson, Jan-Ake
通讯作者：
Gustafsson, Jan-Ake
影响因子：
2.7
作者：
Barbiero, Janaina K.;Santiago, Ronise M.;Vital, Maria A. B. F.
通讯作者：
Vital, Maria A. B. F.
影响因子：
3.5
作者：
Chow, Vivian W.;Mattson, Mark P.;Wong, Philip C.;Gleichmann, Marc
通讯作者：
Gleichmann, Marc