Kinetin Ribosideand Its ProTides Activate the Parkinson’sDisease Associated PTEN-Induced Putative Kinase 1 (PINK1) Independentof Mitochondrial Depolarization

摘要

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.