Remyelination in neuromyelitis optica spectrum disorder is promoted by edaravone through mTORC1 signaling activation

Abstract

Neuromyelitis optica spectrum disorder (NMOSD) is a severe inflammatory autoimmune disease of the central nervous system that is manifested as secondary myelin loss. Oligodendrocyte progenitor cells (OPCs) are the principal source of myelinating oligodendrocytes (OLs) and are abundant in demyelinated regions of NMOSD patients, thus possibly representing a cellular target for pharmacological intervention.

CHI3L1 signaling impairs hippocampal neurogenesis and cognitive function in autoimmune-mediated neuroinflammation

“…2A and table S2; healthy controls: 95.5 ± 43.4 ng/ml, NMO: 143.8 ± 54.2 ng/ml). In addition, as we described earlier, we performed immunohistochemical examinations on biopsied live brain tissues from our prior study ( 33 , 49 ) including one NMO patient and one non-NMO control of head trauma patient (table S3). In addition to the characteristic reduction of AQP4 expression within the end-feet of astrocytes (along the vasculature labeled by endothelial marker CD31), we found that nearly all astrocytes (labeled with GFAP) were positive for CHI3L1 ( Fig.…”

“…Frozen sections of human brain were obtained from biopsy brain tissues of one AQP4-IgG serum-positive NMO patient and one control. The clinical characteristic data of the pathological specimen providers are shown in table S3, and other details were reported in our prior studies ( 33 , 49 ).…”

“…Prompted by our prior studies on NSC differentiation and inflammatory signaling mechanism (33)(34)(35), we decided to focus on NSCs and aimed at illustrating a distinct cellular signaling mechanism of CHI3L1 as the proof of concept for a fundamental CHI3L1 function in the brain.…”

“…The inflammatory cytokines and other factors secreted by activated glia in the microenvironment have been shown to account for such inhibitory effects ( 29 – 32 ). Prompted by our prior studies on NSC differentiation and inflammatory signaling mechanism ( 33 – 35 ), we decided to focus on NSCs and aimed at illustrating a distinct cellular signaling mechanism of CHI3L1 as the proof of concept for a fundamental CHI3L1 function in the brain.…”

Oxidative Stress: A Suitable Therapeutic Target for Optic Nerve Diseases?

“…A recent publication investigated the effects of edaravone, previously mentioned, in cultures and mice with neuromyelitis optica spectrum disorder, and found that it promoted remyelination through activation of the mTOR complex I (mTORC1) signaling pathway [464]. Currently, there is an ongoing trial (NCT05540262) that aims to assess the impact of edaravone in patients with optic neuritis who are positive for aquaporin-4 antibodies.…”