Kinetin Riboside and Its ProTides Activate the Parkinson’s Disease Associated PTEN-Induced Putative Kinase 1 (PINK1) Independent of Mitochondrial Depolarization

[Image: see text] Since loss of function mutations of PINK1 lead to early onset Parkinson’s disease, there has been growing interest in the discovery of small molecules that amplify the kinase activity of PINK1. We herein report the design, synthesis, serum stability, and hydrolysis of four kinetin...

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Detalles Bibliográficos
Autores principales: Osgerby, Laura, Lai, Yu-Chiang, Thornton, Peter J., Amalfitano, Joseph, Le Duff, Cécile S., Jabeen, Iqra, Kadri, Hachemi, Miccoli, Ageo, Tucker, James H. R., Muqit, Miratul M. K., Mehellou, Youcef
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2017
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5410652/
https://www.ncbi.nlm.nih.gov/pubmed/28323427
http://dx.doi.org/10.1021/acs.jmedchem.6b01897
Descripción
Sumario:[Image: see text] Since loss of function mutations of PINK1 lead to early onset Parkinson’s disease, there has been growing interest in the discovery of small molecules that amplify the kinase activity of PINK1. We herein report the design, synthesis, serum stability, and hydrolysis of four kinetin riboside ProTides. These ProTides, along with kinetin riboside, activated PINK1 in cells independent of mitochondrial depolarization. This highlights the potential of modified nucleosides and their phosphate prodrugs as treatments for neurodegenerative diseases.

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