Influence of Sox protein SUMOylation on neural development and regeneration

Abstract

SRY-related HMG-box (Sox) transcription factors are known to regulate central nervous system development and are involved in several neurological diseases. Post-translational modification of Sox proteins is known to alter their functions in the central nervous system. Among the different types of post-translational modification, small ubiquitin-like modifier (SUMO) modification of Sox proteins has been shown to modify their transcriptional activity. Here, we review the mechanisms of three Sox proteins in neuronal development and disease, along with their transcriptional changes under SUMOylation. Across three species, lysine is the conserved residue for SUMOylation. In Drosophila , SUMOylation of SoxN plays a repressive role in transcriptional activity, which impairs central nervous system development. However, deSUMOylation of SoxE and Sox11 plays neuroprotective roles, which promote neural crest precursor formation in Xenopus and retinal ganglion cell differentiation as well as axon regeneration in the rodent. We further discuss a potential translational therapy by SUMO site modification using AAV gene transduction and Clustered regularly interspaced short palindromic repeats-Cas9 technology. Understanding the underlying mechanisms of Sox SUMOylation, especially in the rodent system, may provide a therapeutic strategy to address issues associated with neuronal development and neurodegeneration.

Aldose reductase inhibition decelerates optic nerve degeneration by alleviating retinal microglia activation

“…However, it cannot stop injured axons from dying in a long run. Growing studies of gene therapy show enhancing RGC survival and long-distance axon regeneration 12,[83][84][85] , however, the functional restoration in the visual circuit remains a challenge. For example, a combinational strategy using AR inhibitor and shKLF9/Sox11, known axon regeneration promotors, might provide synergistic effects on axon regeneration.…”