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Calpain-1, not Calpain-2, has relationship with HMGB1/TLR4/NF-ΚB signalling pathway variables in multiple sclerosis
Firdevs Uluc1, Sule Aydin Turkoglu2, Bihter Gokce Celik1
1Department of Interdisciplinary Neuroscience, Institute of Health Sciences, Bolu Abant İzzet Baysal University, Bolu, Turkey.
Neurological Research
|August 24, 2025
Summary
Calpain-1 and Calpain-2 levels are elevated in patients with Multiple Sclerosis (MS) and Neuromyelitis Optica Spectrum Disorder (NMOSD), suggesting a role in neuroinflammation via the HMGB1 pathway.
Area of Science:
- Neuroimmunology
- Neuroinflammation
- Demyelinating Diseases
Background:
- Understanding signaling pathways is critical for demyelinating diseases like MS and NMOSD.
- The HMGB1/TLR4/NF-κB pathway is implicated in neuroinflammation.
Purpose of the Study:
- To investigate the relationship between Calpain-1 (CAPN1) and Calpain-2 (CAPN2) and the HMGB1/TLR4/NF-κB pathway.
- To compare these markers in patients with Multiple Sclerosis (pwMS) and Neuromyelitis Optica Spectrum Disorder (pwNMOSD).
Main Methods:
- ELISA was used to measure levels of CAPN1, CAPN2, HMGB1, soluble TLR4 (sTLR4), and NF-κB.
- Study included 36 pwMS, 9 pwNMOSD, and 28 controls (pwPTC).
Main Results:
- pwMS exhibited significantly higher levels of CAPN1 and CAPN2 compared to pwNMOSD and controls.
- No significant differences were observed in HMGB1, sTLR4, or NF-κB levels between groups.
- Positive correlations were found between CAPN1 and CAPN2 in pwMS, and between CAPN1 and HMGB1 in pwMS.
Conclusions:
- CAPN1 may contribute to neuroinflammation in MS through HMGB1 signaling.
- Further research with larger cohorts and longitudinal studies is warranted.
- Investigating CAPN1 inhibition could offer therapeutic insights for MS.
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