Circular RNAs: The Novel Actors in Pathophysiology of Spinal Cord Injury.

Cynthia Sámano,Miranda Mladinic,Graciela L Mazzone

doi:10.3389/fnint.2021.758340

Abstract

Spinal Cord Injury (SCI) can elicit a progressive loss of nerve cells promoting disability, morbidity, and even mortality. Despite different triggering mechanisms, a cascade of molecular events involving complex gene alterations and activation of the neuroimmune system influence either cell damage or repair. Effective therapies to avoid secondary mechanisms underlying SCI are still lacking. The recent progression in circular RNAs (circRNAs) research has drawn increasing attention and opened a new insight on SCI pathology. circRNAs differ from traditional linear RNAs and have emerged as the active elements to regulate gene expression as well as to facilitate the immune response involved in pathophysiology-related conditions. In this review, we focus on the impact and possible close relationship of circRNAs with pathophysiological mechanisms following SCI, where circRNAs could be the key transcriptional regulatory molecules to define neuronal death or survival. Advances in circRNAs research provide new insight on potential biomarkers and effective therapeutic targets for SCI patients.

Highlights

Circular RNAs are endogenous single-stranded RNA molecules produced by circularization events (Guo et al, 2014; Wang et al, 2014), shown to be very stable and conserved functional molecules, highly expressed in the central nervous system (CNS; Memczak et al, 2013; Rybak-Wolf et al, 2015). circRNAs play crucial regulatory roles in gene expression at the posttranscriptional level (Zhang et al, 2013; Chen, 2020) and are closely associated with multiple neurodegenerative diseases, especially at the level of the neuro-immune pathways (Qu et al, 2020; Xu et al, 2021)
It is possible that circRNAs may play important role in molecular events involved in spinal cord injury (SCI) pathology
CircRNAs in Pathophysiology of Spinal Cord circRNAs have been recently shown to be involved in the pathogenesis and promotion of neuro-inflammation, including the altered expression of circRNAs in critical stages of SCI physiopathology (Qin et al, 2019; Zhou et al, 2019)

Summary

INTRODUCTION

Circular RNAs (circRNAs) are endogenous single-stranded RNA molecules produced by circularization events (Guo et al, 2014; Wang et al, 2014), shown to be very stable and conserved functional molecules, highly expressed in the central nervous system (CNS; Memczak et al, 2013; Rybak-Wolf et al, 2015). circRNAs play crucial regulatory roles in gene expression at the posttranscriptional level (Zhang et al, 2013; Chen, 2020) and are closely associated with multiple neurodegenerative diseases, especially at the level of the neuro-immune pathways (Qu et al, 2020; Xu et al, 2021). It is possible that circRNAs may play important role in molecular events involved in spinal cord injury (SCI) pathology. Either traumatic or non-traumatic, SCIs start with primary insult, followed by subsequent secondary pathological events that amplify spinal neurodegeneration (Quadri et al, 2020). Current treatments exhibit limited efficacy for complete functional recovery after SCI (Martirosyan, 2021), mostly because of the poor understanding of molecular events underlying secondary injury. CircRNAs in Pathophysiology of Spinal Cord circRNAs have been recently shown to be involved in the pathogenesis and promotion of neuro-inflammation, including the altered expression of circRNAs in critical stages of SCI physiopathology (Qin et al, 2019; Zhou et al, 2019). The aim of this review is to highlight the intriguing expression of circRNAs after SCI where they could play a paramount role in neurodegeneration and offer new therapeutic targets

CHARACTERISTICS OF circRNAs

PHARMACOLOGICAL INTERVENTIONS AND circRNAs

CONCLUSIONS

Findings

AUTHOR CONTRIBUTIONS