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Neuroprotection of CK-1 inhibitors against TDP-43 and LPS toxicity

AuthorsMartínez, Ana ; Pérez, Daniel I.; Salado, Irene G. ; Gil, Carmen ; Morales-García, José A. ; Pérez Castillo, Ana
Issue Date2015
CitationAD/PD 2015
Abstract[Objectives]: To show that protein kinase CK-1 inhibitors are useful innovative drug candidates for TDP-43 mediated neurodegenerative diseases and also Parkinson disease. [Methods]: Chemical genetics approach to identify new CK-1 inhibitors using an in-house chemical library of heterocyclic small molecules. Hit to lead optimization trough medicinal chemistry programs. Lead to candidate selection based on ADME-Tox properties. Cell based and animal studies with leads and candidates to confirm the efficacy of CK-1 inhibitors. [Results]: Identification of two new families of CK-1 inhibitors. A reduction of TDP-43 phosphorylation is observed after CK-1 inhibitors treatment in cell cultures. Neuronal toxicity induced by hTDP-43 protein on transgenic flies is decreased after the treatment with our CK-1 inhibitors. CK-1 inhibitors also shown neuroprotection in cell based and in vivo models of Parkinson disease. [Conclusions]: CK-1 inhibitors, and specially our small molecule candidate IGS2.7, are promising drug candidates for the future treatment of neurodegenerative diseases such as Alzheimer disease, amyotrophic lateral sclerosis, frontotemporal dementia and Parkinson disease.
DescriptionResumen del trabajo presentado a la 12th International Conference on Alzheimer's & Parkinson's Diseases, celebrada en Niza (Francia ) del 18 al 22 de marzo de 2015.
Appears in Collections:(IIBM) Comunicaciones congresos
(CIB) Comunicaciones congresos
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