The Anthelmintic Drug Niclosamide and Its Analogues Activate the Parkinson's Disease Associated Protein Kinase PINK1.
The Anthelmintic Drug Niclosamide and Its Analogues Activate the Parkinson's Disease Associated Protein Kinase PINK1.
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DOI：
10.1002/cbic.201700500
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发表时间：
2018-03-02
期刊：
影响因子：
--
通讯作者：
Muqit MMK
中科院分区：
文献类型：
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作者：
Barini E;Miccoli A;Tinarelli F;Mulholland K;Kadri H;Khanim F;Stojanovski L;Read KD;Burness K;Blow JJ;Mehellou Y;Muqit MMK
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）的病因。各种研究表明，激活PINK1可能是治疗神经退行性疾病（如PD）的一种有用策略。在此，显示了驱蠕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PINK 1。使用这些化合物，首次证明PINK1通路在原代神经元中是活跃的和可检测的。这些研究结果表明，氯硝柳胺及其类似物是研究PINK1通路的稳健化合物，并可能有望成为PD和相关疾病的治疗策略。
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.
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影响因子：
7.7
作者：
Kazlauskaite A;Martínez-Torres RJ;Wilkie S;Kumar A;Peltier J;Gonzalez A;Johnson C;Zhang J;Hope AG;Peggie M;Trost M;van Aalten DM;Alessi DR;Prescott AR;Knebel A;Walden H;Muqit MM
通讯作者：
Muqit MM
DOI：
10.1158/1078-0432.ccr-15-2256
发表时间：
2016-07-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Satoh K;Zhang L;Zhang Y;Chelluri R;Boufraqech M;Nilubol N;Patel D;Shen M;Kebebew E
通讯作者：
Kebebew E
影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1083/jcb.201402104
发表时间：
2014-04-28
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kane LA;Lazarou M;Fogel AI;Li Y;Yamano K;Sarraf SA;Banerjee S;Youle RJ
通讯作者：
Youle RJ
影响因子：
82.9
作者：
通讯作者：
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