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

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...

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Autores principales: Barini, Erica, Miccoli, Ageo, Tinarelli, Federico, Mulholland, Katie, Kadri, Hachemi, Khanim, Farhat, Stojanovski, Laste, Read, Kevin D., Burness, Kerry, Blow, Julian J., Mehellou, Youcef, Muqit, Miratul M. K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5901409/
https://www.ncbi.nlm.nih.gov/pubmed/29226533
http://dx.doi.org/10.1002/cbic.201700500
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author Barini, Erica
Miccoli, Ageo
Tinarelli, Federico
Mulholland, Katie
Kadri, Hachemi
Khanim, Farhat
Stojanovski, Laste
Read, Kevin D.
Burness, Kerry
Blow, Julian J.
Mehellou, Youcef
Muqit, Miratul M. K.
author_facet Barini, Erica
Miccoli, Ageo
Tinarelli, Federico
Mulholland, Katie
Kadri, Hachemi
Khanim, Farhat
Stojanovski, Laste
Read, Kevin D.
Burness, Kerry
Blow, Julian J.
Mehellou, Youcef
Muqit, Miratul M. K.
author_sort Barini, Erica
collection PubMed
description 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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spelling pubmed-59014092018-04-24 The Anthelmintic Drug Niclosamide and Its Analogues Activate the Parkinson's Disease Associated Protein Kinase PINK1 Barini, Erica Miccoli, Ageo Tinarelli, Federico Mulholland, Katie Kadri, Hachemi Khanim, Farhat Stojanovski, Laste Read, Kevin D. Burness, Kerry Blow, Julian J. Mehellou, Youcef Muqit, Miratul M. K. Chembiochem Communications 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. John Wiley and Sons Inc. 2018-01-24 2018-03-02 /pmc/articles/PMC5901409/ /pubmed/29226533 http://dx.doi.org/10.1002/cbic.201700500 Text en © 2018 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Communications
Barini, Erica
Miccoli, Ageo
Tinarelli, Federico
Mulholland, Katie
Kadri, Hachemi
Khanim, Farhat
Stojanovski, Laste
Read, Kevin D.
Burness, Kerry
Blow, Julian J.
Mehellou, Youcef
Muqit, Miratul M. K.
The Anthelmintic Drug Niclosamide and Its Analogues Activate the Parkinson's Disease Associated Protein Kinase PINK1
title The Anthelmintic Drug Niclosamide and Its Analogues Activate the Parkinson's Disease Associated Protein Kinase PINK1
title_full The Anthelmintic Drug Niclosamide and Its Analogues Activate the Parkinson's Disease Associated Protein Kinase PINK1
title_fullStr The Anthelmintic Drug Niclosamide and Its Analogues Activate the Parkinson's Disease Associated Protein Kinase PINK1
title_full_unstemmed The Anthelmintic Drug Niclosamide and Its Analogues Activate the Parkinson's Disease Associated Protein Kinase PINK1
title_short The Anthelmintic Drug Niclosamide and Its Analogues Activate the Parkinson's Disease Associated Protein Kinase PINK1
title_sort anthelmintic drug niclosamide and its analogues activate the parkinson's disease associated protein kinase pink1
topic Communications
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5901409/
https://www.ncbi.nlm.nih.gov/pubmed/29226533
http://dx.doi.org/10.1002/cbic.201700500
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