Small molecules targeting glycogen synthase kinase 3 as potential drug candidates for the treatment of retinitis pigmentosa

Abstract

Retinitis pigmentosa (RP) is an inherited retinal dystrophy that courses with progressive degeneration of retinal tissue and loss of vision. Currently, RP is an unpreventable, incurable condition. We propose glycogen synthase kinase 3 (GSK-3) inhibitors as potential leads for retinal cell neuroprotection, since the retina is also a part of the central nervous system and GSK-3 inhibitors are potent neuroprotectant agents. Using a chemical genetic approach, diverse small molecules with different potency and binding mode to GSK-3 have been used to validate and confirm GSK-3 as a pharmacological target for RP. Moreover, this medicinal chemistry approach has provided new leads for the future disease-modifying treatment of RP.

Keywords:

• GSK-3 inhibitors
• retinal diseases
• retinitis pigmentosa
• glaucoma

Acknowledgements

JZD acknowledges a pre-doc grant in the FPU program to the Spanish MECD.

Disclosure statement

The authors report no conflict of interest.

Additional information

Funding

This work has been partially funded by the Spanish MINECO grants (SAF2012-37979-C03-01 to AM and SAF2013-41059-R to EJdlR).