The Anthelmintic Drug Niclosamide and Its Analogues Activate the Parkinson's Disease Associated Protein Kinase PINK1 |
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| Authors: | Dr Erica Barini Ageo Miccoli Dr Federico Tinarelli Katie Mulholland Dr Hachemi Kadri Dr Farhat Khanim Dr Laste Stojanovski Dr Kevin D Read Kerry Burness Prof Julian J Blow Dr Youcef Mehellou Dr Miratul M K Muqit |
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| Affiliation: | 1. MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee, UK;2. School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, UK;3. Centre for Gene Regulation and Expression, University of Dundee, Dundee, UK;4. School of Biosciences, University of Birmingham, Birmingham, UK;5. Drug Discovery Unit, University of Dundee, Dundee, UK;6. MRC PPU Reagents and Services, University of Dundee, Dundee, UK;7. School of Medicine, University of Dundee, Dundee, UK |
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| Abstract: | 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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| Keywords: | drug discovery membranes mitochondria neurodegenerative diseases proteins |
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