The anthelmintic drug niclosamide and its analogues activate the Parkinson's disease associated protein kinase PINK1

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, we show that the anthelmintic drug niclosamide and its analogues are capable of activating PINK1 in cells via reversible impairment of the mitochondrial membrane potential. Using these compounds, we demonstrate for the first time that the PINK1 pathway is active and detectable in primary neurons. Our findings suggest that niclosamide and its analogues are robust compounds to study the PINK1 pathway and may hold promise as a therapeutic strategy in Parkinson's and related disorders