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 (Lead / Corresponding author), Miratul M.K. Muqit (Lead / Corresponding author)

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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 languageEnglish
Pages (from-to)425-429
Number of pages5
JournalChemBioChem
Volume19
Issue number5
Early online date10 Dec 2017
DOIs
Publication statusPublished - 2 Mar 2018

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Niclosamide
Anthelmintics
Protein Kinases
Parkinson Disease
Mitochondrial Membrane Potential
Parkinsonian Disorders
Neurodegenerative Diseases
Pharmaceutical Preparations
Neurodegenerative diseases
Phosphotransferases
Neurons
Mutation
Chemical activation
Membranes
Parkinson Disease Associated Proteins
Therapeutics

Keywords

  • Drug discovery
  • Membranes
  • Mitochondria
  • Neurodegenerative diseases
  • Proteins

Cite this

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. In: ChemBioChem. 2018 ; Vol. 19, No. 5. pp. 425-429.
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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 (Lead / Corresponding author); Muqit, Miratul M.K. (Lead / Corresponding author).

In: ChemBioChem, Vol. 19, No. 5, 02.03.2018, p. 425-429.

Research output: Contribution to journalArticle

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AU - Barini, Erica

AU - Miccoli, Ageo

AU - Tinarelli, Federico

AU - Mulholland, Katie

AU - Kadri, Hachemi

AU - Khanim, Farhat

AU - Stojanovski, Laste

AU - Read, Kevin D.

AU - Burness, Kerry

AU - Blow, Julian J.

AU - Mehellou, Youcef

AU - Muqit, Miratul M.K.

N1 - Funding: Wellcome Trust. Grant Numbers: WT096598MA, 101022/Z/13/Z; Medical Research Council. Grant Number: MC_PC_16041.

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