Biological and Pharmacological Characterization of Benzothiazole-Based CK-1δ Inhibitors in Models of Parkinson's Disease

ACS Omega
J A Morales-GarcíaD I Pérez

Abstract

Parkinson's disease (PD), an age-related neurodegenerative disorder that results from a progressive loss of dopaminergic neurons has an enormous economical and human cost. Unfortunately, only symptomatic treatment such as dopamine replacement therapy is available. Therefore, drugs with new mechanisms of action able to protect against neuronal cell death are an urgent need. We here report the in vivo efficacy on dopaminergic neuronal protection in a PD mouse model and the lack of toxicity in zebrafish and Ames test of benzothiazole-based casein kinase-1δ (CK-1δ) nanomolar inhibitors. On the basis of these results, we propose protein kinase CK-1δ inhibitors as the possible disease-modifying drugs for PD, benzothiazole 4 being a promising drug candidate for further development as a new therapy of this neurodegenerative disease.

References

Nov 1, 1972·Proceedings of the National Academy of Sciences of the United States of America·B N AmesH Bartsch
Jan 5, 2000·The Journal of Biological Chemistry·M OkochiC Haass
Aug 20, 2008·Fundamental & Clinical Pharmacology·Garima DuttaBin Liu
Jun 26, 2010·Medicinal Research Reviews·Daniel I PerezAna Martinez
Nov 23, 2012·ACS Chemical Neuroscience·Jose A Morales-GarciaAna Perez-Castillo
Feb 21, 2013·ACS Chemical Neuroscience·J A Morales-GarcíaA Pérez-Castillo
Jan 17, 2014·Zebrafish·Sridhara ChakravarthySunil Kumar Sukumaran
Mar 7, 2014·Journal of Medicinal Chemistry·Irene G SaladoDaniel I Perez
Oct 2, 2014·ACS Chemical Neuroscience·A Connor WhitfieldR Nathan Daniels

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Citations

Apr 14, 2020·Aging·Yu-Chen LinChun-Han Chen
Nov 13, 2020·Molecular Diversity·Ayushi SethiyaShikha Agarwal
Oct 30, 2020·Frontiers in Aging Neuroscience·Caroline L Benn, Lee A Dawson

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