The Anthelmintic Drug Niclosamide and Its Analogues Activate the Parkinson's Disease Associated Protein Kinase PINK1

Erica Barini; Ageo Miccoli; Federico Tinarelli; Katie Mulholland; Hachemi Kadri; Farhat Khanim; Laste Stojanovski; Kevin D. Read; Kerry Burness; Julian J. Blow; Youcef Mehellou; Miratul M. K. Muqit

doi:10.1002/cbic.201700500

The Anthelmintic Drug Niclosamide and Its Analogues Activate the Parkinson's Disease Associated Protein Kinase PINK1

Erica Barini, Ageo Miccoli, Federico Tinarelli, Katie Mulholland, Hachemi Kadri, Farhat Khanim, Laste Stojanovski, Kevin D. Read, Kerry Burness, Julian J. Blow, Youcef Mehellou, Miratul M. K. Muqit

Biosciences

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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.

Original language	English
Pages (from-to)	425-429
Number of pages	5
Journal	ChemBioChem
Volume	19
Issue number	5
Early online date	24 Jan 2018
DOIs	https://doi.org/10.1002/cbic.201700500
Publication status	Published - 2 Mar 2018

Keywords

Journal Article
drug discovery
membranes
mitochondria
neurodegenerative diseases
proteins

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10.1002/cbic.201700500Licence: Creative Commons: Attribution (CC BY)

Barini_Anthelmintic_Drug_Niclosamide_ChemBioChem
This is the version of record of the following article: Erica Barini, Ageo Miccoli, Federico Tinarelli, Katie Mulholland, Hachemi Kadri, Farhat Khanim, Laste Stojanovski, Kevin D. Read, Kerry Burness, Julian J. Blow, Youcef Mehellou and Miratul M. K. Muqit, which has been published at https://doi.org/10.1002/cbic.201700500. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.
Final published version, 777 KBLicence: Creative Commons: Attribution (CC BY)

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Barini, E., Miccoli, A., Tinarelli, F., Mulholland, K., Kadri, H., Khanim, F., Stojanovski, L., Read, K. D., Burness, K., Blow, J. J., Mehellou, Y., & Muqit, M. M. K. (2018). The Anthelmintic Drug Niclosamide and Its Analogues Activate the Parkinson's Disease Associated Protein Kinase PINK1. ChemBioChem, 19(5), 425-429. Advance online publication. https://doi.org/10.1002/cbic.201700500

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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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AU - Mulholland, Katie

AU - Kadri, Hachemi

AU - Khanim, Farhat

AU - Stojanovski, Laste

AU - Read, Kevin D.

AU - Burness, Kerry

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AU - Mehellou, Youcef

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AB - 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.

KW - Journal Article

KW - drug discovery

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The Anthelmintic Drug Niclosamide and Its Analogues Activate the Parkinson's Disease Associated Protein Kinase PINK1

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