GSK-3 inhibitors as new leads for Parkinson's disease pharmacotherapy

Póster presentado a la "10th International Conference on Alzheimer's & Parkinson's Diseases" celebrada del 9 al 13 de marzo de 2011 en Barcelona (España).Parkinson's disease (PD) is a devastating neurodegenerative disorder characterized by degeneration of the nigrostriatal dopaminergic pathway. As the current therapies only lead to temporarily limited improvement, and have side effects, new approaches to treat Parkinson disease need to be developed. To discover new leads for further pharmaceutical development we have screened our in-house chemical library on a well-established cellular model of PD. In depth in vitro studies to look for the mechanism of action of the selected compounds are pursued. From the screening of more than 400 chemically diverse molecules, we have selected 15 compounds for more in deep analysis. After different enzymatic assays we found that SC001 is a GSK-3 inhibitor with an IC50=3,38 M. Based on this, we have evaluated other chemically different GSK-3 inhibitors, many of them synthesized in our laboratory [1, 2], as potential neuroprotective agents for PD. Our results show that SC001 and other GSK-3 inhibitors have neuroprotective and anti-inflammatory effects in vitro. Furthermore, SC001 protected dopa-minergic neurons and reduced microglia activation in an in vivo model of PD.Peer Reviewe