Is GSK3 a relevant target for the treatment of retinal degeneration?
Is GSK3 a relevant target for the treatment of retinal degeneration? Neurodegenerative diseases represent a major health problem in the aging population. Glycogen synthase kinase 3 (GSK3) is often implicated and its pharmacological inhibition constitutes a promising treatment, in particular for Alzheimer’s or Parkinson’s diseases. We have investigated, in a review article published in Cells, the potential of this kinase as a therapeutic target in neurodegenerative diseases of the retina, such as glaucoma or age-related macular degeneration (AMD). We present the state of the art of the role of GSK3 in the retina. This shows that this kinase plays a key role in cellular processes known to be deregulated in patients with retinal dystrophies, such as glucose homeostasis, which is critical for photoreceptor survival, or oxidative stress, a major component of retinal degeneration. Inhibiting GSK3 could therefore have neuroprotective effects. Inhibiting GSK3 could also have beneficial effects on inflammation. On the other hand, GSK3 would have to be activated to slow down the neovascularization that is observed in some retinal degenerations, such as diabetic retinopathy or wet AMD.
Thus, although GSK3 inhibitors are promising, the involvement of GSK3 kinase in a large number of cellular pathways means that the use of these therapeutic agents could lead to adverse effects. The challenge is therefore to identify GSK3 targets that could be the basis for the development of new therapeutic approaches targeting more specifically the biological processes deregulated in the different retinal diseases.
GSK3 Is a Central Player in Retinal Degenerative Diseases but a Challenging Therapeutic Target. Catherine Hottin, Muriel Perron, and Jérôme E. Roger.