Calpain-1, not Calpain-2, has relationship with HMGB1/TLR4/NF-ΚB signalling pathway variables in multiple sclerosis.

IF 1.5 4区医学 Q3 CLINICAL NEUROLOGY

Neurological Research Pub Date : 2025-08-24 DOI:10.1080/01616412.2025.2551093

Firdevs Uluc, Sule Aydin Turkoglu, Bihter Gokce Celik, Seyda Karabörk, Seyit Ali Kayis

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引用次数: 0

Abstract

Background: Identification of the related signalling pathways is very crucial for demyelinating diseases.

Objectives: The aim of this study was to investigate the relation between Calpain-1 (CAPN1) and Calpain-2 (CAPN2) with the HMGB1/TLR4/NF-κB signaling pathway in patients with Multiple Sclerosis (pwMS) and Neuromyelitis Optica Spectrum Disorder (pwNMOSD).

Methods: We recruited 45 newly diagnosed patients during the relapse period, comprising 36 pwMS and 9 pwNMOSD. Twenty-eight patients with pseudotumor cerebri (pwPTC) were recruited as control. CAPN1, CAPN2, HMGB1, soluble TLR4 (sTLR4), NF-κB levels were compared between the groups by ELISA technique.

Results: pwMS had higher levels of CAPN1 than those with pwNMOSD and pwPTC. Similarly, pw MS had a considerably greater level of CAPN2 than pwPTC and pwNMOSD. Between the groups, there were no variations in HMGB1, sTLR4, NF-κB, and IL-37 levels. The CAPN1 and CAPN2 levels in the pwMS showed a favorable correlation. In pwMS, CAPN1 and HMGB1 also showed a positive correlation.

Conclusions: This study proposes a valuable and novel perspective on the pathophysiology of MS, placing CAPN1 as a potentially important contributor to neuroinflammatory signalling via HMGB1. Future research should aim to validate these findings using larger, balanced cohorts and include longitudinal CSF and serum analysis. Experimental in vitro or in vivo studies investigating CAPN1 inhibition and its impact on HMGB1-related signalling are necessary to explore therapeutic implications.

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在多发性硬化症中，与HMGB1/TLR4/NF-ΚB信号通路变量相关的是Calpain-1，而不是Calpain-2。

背景：识别相关信号通路对脱髓鞘疾病至关重要。目的：探讨多发性硬化症（Multiple Sclerosis, pwMS）和视神经脊髓炎（neuromyeltis Optica Spectrum Disorder, pwNMOSD）患者中Calpain-1 （CAPN1）和Calpain-2 （CAPN2）与HMGB1/TLR4/NF-κB信号通路的关系。方法：我们招募了45例复发期新诊断的患者，其中pwMS 36例，pwNMOSD 9例。选取28例假性脑瘤（pwPTC）患者作为对照。ELISA法比较各组间CAPN1、CAPN2、HMGB1、可溶性TLR4 （sTLR4）、NF-κB水平。结果：pwMS患者的CAPN1水平高于pwNMOSD和pwPTC患者。同样，pw MS的CAPN2水平明显高于pwPTC和pwNMOSD。两组间HMGB1、sTLR4、NF-κB、IL-37水平均无差异。在pwMS中，CAPN1和CAPN2水平呈良好的相关性。在pwMS中，CAPN1与HMGB1也呈正相关。结论：本研究为MS的病理生理学提供了一个有价值的新视角，将CAPN1作为通过HMGB1进行神经炎症信号传导的潜在重要贡献者。未来的研究应该旨在通过更大的、平衡的队列来验证这些发现，并包括纵向CSF和血清分析。研究CAPN1抑制及其对hmgb1相关信号的影响的体外或体内实验研究对于探索治疗意义是必要的。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neurological Research 医学-临床神经学

CiteScore

3.60

自引率

0.00%

发文量

116

审稿时长

5.3 months

期刊介绍： Neurological Research is an international, peer-reviewed journal for reporting both basic and clinical research in the fields of neurosurgery, neurology, neuroengineering and neurosciences. It provides a medium for those who recognize the wider implications of their work and who wish to be informed of the relevant experience of others in related and more distant fields. The scope of the journal includes: •Stem cell applications •Molecular neuroscience •Neuropharmacology •Neuroradiology •Neurochemistry •Biomathematical models •Endovascular neurosurgery •Innovation in neurosurgery.