Investigation of the relationship between calpain and HMGB1/TLR4/NF-κB signaling pathway in multiple sclerosis and other demyelinating diseases

Identification of signaling pathways and their associated factors is crucial for finding more effective treatments for demyelinating diseases. Accordingly, it was aimed to investigate the possible relationship between Calpain-1 (CLPN1) and Calpain-2 (CLPN2) and HMGB1/TLR4/NF-κB signaling pathway and to determine the effect of these proteins on Interleukin 17A (IL-17A) and Interleukin 37 (IL-37) cytokines in newly diagnosed Multiple Sclerosis (MS) and Neuromyelitis Optica Spectrum Disorder (NMOSD) patients. CLPN1, CLPN2, HMGB1, TLR4, NF-κB, IL-17A and IL-37 levels were determined by ELISA method in CSF samples of newly diagnosed MS (n=36), NMOSD (n=9) and Pseudotumor Cerebri (PTS, n=28) patients aged between 18-65 years who applied to BAİBÜ Neurology outpatient clinic. CLPN1 level is higher in the MS group than in the NMOSD and PTS groups. CLPN2 levels were higher in the MS group than in the PTS group and lower in the NMOSD group than in the PTS group. There were no significant differences in HMGB1, TLR4, NF-κB, IL-17A and IL 37 levels between the groups. However, a positive correlation was observed between IL-17A and IL-37. No significant difference was observed in all parameters depending on age and gender. A positive correlation was observed between CLPN1 and HMGB1/TLR4/NF-κB signaling pathway in MS patients. Also, a positive correlation was observed between CLPN2 and HMGB1 and TLR4, but not with NF-κB. There was no correlation between HMGB1/TLR4/NF κB signaling pathway with CLPN1 and CLPN2 in NMOSD cases. IL-37 level was higher than IL-17A in all groups. As a result of these results, the high level of anti-infilammatory IL-37 in all groups may be thought to be due to the high level of CLPN1, reported to be neuroprotective. It may be considered that CLPN1 is more effective than CLPN2 in the early phase of neuroinflammation. In-vivo and in-vitro prospective studies with CLPN1-specific inhibitors in larger study groups are recommended to determine the difference in CLPN1 and CLPN2 effects and the relationship with HMGB1/TLR4/NF-κB signaling pathway with more precise data.