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The Anthelmintic Drug Niclosamide and Its Analogues Activate the Parkinson's Disease Associated Protein Kinase PINK1.
ChemBioChem ( IF 3.2 ) Pub Date : 2018-01-24 , DOI: 10.1002/cbic.201700500
Erica Barini 1 , Ageo Miccoli 2 , Federico Tinarelli 3 , Katie Mulholland 1 , Hachemi Kadri 2 , Farhat Khanim 4 , Laste Stojanovski 5 , Kevin D Read 5 , Kerry Burness 6 , Julian J Blow 3 , Youcef Mehellou 2 , Miratul M K Muqit 1, 7
Affiliation  

Mutations in PINK1, which impair its catalytic kinase activity, are causal for autosomal recessive early-onset Parkinson's disease (PD). Various studies have indicated that the activation of PINK1 could be a useful strategy in treating neurodegenerative diseases, such as PD. Herein, it is shown that the anthelmintic drug niclosamide and its analogues are capable of activating PINK1 in cells through the reversible impairment of the mitochondrial membrane potential. With these compounds, for the first time, it is demonstrated that the PINK1 pathway is active and detectable in primary neurons. These findings suggest that niclosamide and its analogues are robust compounds for the study of the PINK1 pathway and may hold promise as a therapeutic strategy in PD and related disorders.

中文翻译:

驱虫药氯硝柳胺及其类似物可激活帕金森病相关蛋白激酶 PINK1。

PINK1 的突变会损害其催化激酶活性,是常染色体隐性遗传早发性帕金森病 (PD) 的原因。各种研究表明,激活 PINK1 可能是治疗 PD 等神经退行性疾病的有用策略。在此,表明驱虫药物氯硝柳胺及其类似物能够通过线粒体膜电位的可逆损伤来激活细胞中的 PINK1。使用这些化合物,首次证明 PINK1 通路在原代神经元中是活跃且可检测的。这些发现表明,氯硝柳胺及其类似物是研究 PINK1 通路的有力化合物,并有望成为 PD 和相关疾病的治疗策略。
更新日期:2018-01-24
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