Protein post-translational modifications after spinal cord injury

Abstract

Deficits in intrinsic neuronal capacities in the spinal cord, a lack of growth support, and suppression of axonal outgrowth by inhibitory molecules mean that spinal cord injury almost always has devastating consequences. As such, one of the primary targets for the treatment of spinal cord injury is to develop strategies to antagonize extrinsic or intrinsic axonal growth-inhibitory factors or enhance the factors that support axonal growth. Among these factors, a series of individual protein level disorders have been identified during the generation of axons following spinal cord injury. Moreover, an increasing number of studies have indicated that post-translational modifications of these proteins have important implications for axonal growth. Some researchers have discovered a variety of post-translational modifications after spinal cord injury, such as tyrosination, acetylation, and phosphorylation. In this review, we reviewed the post-translational modifications for axonal growth, functional recovery, and neuropathic pain after spinal cord injury, a better understanding of which may elucidate the dynamic change of spinal cord injury-related molecules and facilitate the development of a new therapeutic strategy for spinal cord injury.

Keywords: extracellular matrix; function impairment; glial scar; nerve regeneration; neuropathic pain; post-translational modification; spinal cord injury; therapeutic target.

Figure 1

Main factors hindering axon regeneration after spinal cord injury. Diminished neuronal regenerative capacity, glial scar formation, and the accumulation of inhibitory molecules are the factors that most commonly lead to impaired axon regeneration.

Figure 2

Post-translational modifications affect growth cone regeneration after spinal cord injury. Microtubes of the growth cone are modified by phosphorylation, acetylation, tyrosination, and polyglutamylation. HDAC6: Histone deacetylase 6; MAP18: microtubule-associated protein 18; MEC-17: an ortholog of human ATAT1 (alpha tubulin acetyltransferase 1); TTL: tubulin tyrosine ligase; TTLL7: tubulin tyrosine ligase-like 7.