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

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 kinetinriboside 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.

Principal Investigator(s):

Author(s):
Laura Osgerby, Yu-Chiang Lai, Peter J Thornton, Joseph Amalfitano, Cécile S Le Duff, Iqra Jabeen, Hachemi Kadri, Ageo Miccoli, James HR Tucker, Miratul MK Muqit, Youcef Mehellou

PubMed:
28323427
Citation:
Laura Osgerby, Yu-Chiang Lai, Peter J Thornton, Joseph Amalfitano, Cécile S Le Duff, Iqra Jabeen, Hachemi Kadri, Ageo Miccoli, James HR Tucker, Miratul MK Muqit, Youcef Mehellou
J Med Chem.
2017
60(8)
3518-3524.
PMID: 28323427