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

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.

SUBMITTER: Morales-Garcia JA

PROVIDER: S-EPMC6044573 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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

Morales-Garcia José A JA Salado Irene G IG Sanz-San Cristobal Marina M Gil Carmen C Pérez-Castillo Ana A Martínez Ana A Pérez Daniel I DI

ACS omega 20170830 8

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 zebr ...[more]

PMID: 30023743

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