Therapeutic Potential of Wnt-3a in Neurological Recovery after Spinal Cord Injury

Abstract

Background: Spinal cord injury (SCI) is a constant challenge in medical research and a global therapeutic problem. Treatment of this condition remains difficult in clinical practice. Hence, prevention, treatment, and rehabilitation of SCI have become imminent tasks in the medical field. Summary: Recent evidence suggest the important role of Wnt/β-catenin signaling pathway, a canonical Wnt signaling pathway, in neural development, axon guidance, neuropathic pain relief, and neuronal survival. Wnt-3a is regarded as an activator of the canonical Wnt signaling pathway. This activator is expressed in the dorsal midline region and is responsible for spinal cord development. In addition, Wnt-3a plays a regulatory role in autophagy, apoptosis, and regeneration of neurons; neurogenic inflammation; and axon regeneration. Herein, we demonstrated that neuronal autophagy was regulated by Wnt-3a via β-catenin and mammalian target of rapamycin signaling pathways after SCI. Our study also discovered that the Wnt-3a provided a favorable microenvironment for the recovery of nerve function after SCI. Key Messages: This study systematically elaborates the neuroprotective effect of Wnt-3a and its neuroprotection molecular mechanism after SCI. This study provides a new molecular mechanism and research basis for clinical treatment of SCI.

Single nuclei analyses reveal transcriptional profiles and marker genes for diverse supraspinal populations

“…This information is potentially informative in predicting differential responses to cues in the spinal cord environment. We first assembled a list of ligands of interest, based on neurotrophins, growth factors, and axon guidance cues that are either endogenous to spinal cord tissue or which have been exogenously applied in experimental paradigms of spinal injury (Badhiwala et al, 2018; Dun and Parkinson, 2017; Gao et al, 2019; Giger et al, 2010; Goldshmit et al, 2011; Haenzi and Moon, 2017; Hata et al, 2006; Kitamura et al, 2019; Liu et al, 2017; Rosich et al, 2017; Walker and Xu, 2018; Yamane et al, 2019). We then examined the expression of various receptors for each cue across different subtypes of supraspinal neurons ( Figure 9B ).…”

AAV2-mediated and hypoxia response element-directed expression of bFGF in neural stem cells showed therapeutic effects on spinal cord injury in rats

“…Studies have shown that autophagic death of neurons and glial cells plays a role in SCI-induced neuronal damage, and inhibition of autophagy may serve as a therapeutic strategy for SCI 54 . It has been suggested that autophage signaling plays a direct role in inducing cell death in neuronal injury, and exceeding autophagy could result in cell death [55][56][57][58] . P62 is one of the marker proteins that are associated with autophagy activity, and its levels indirectly reflect the degree of autophagy body clearance.…”

Living biobank-based cancer organoids: prospects and challenges in cancer research

“…The Wnt proteins mainly affect stem/progenitor cells by regulating cell proliferation, differentiation, migration, and patterns during development 30 . Wnt-3A, a member of the Wnt family, is an activator of the Wnt/β-catenin pathway 31 and is widely used in many organoid culture media. Wnt-activated organoids show tissue atypia, high proliferation and replication activity, prolonged culturability, and diminished apoptosis 32 .…”