# Do Nitrosative Stress Molecules Hold Promise as Biomarkers for Multiple Sclerosis?

**Authors:** Moritz Förster, Saskia Räuber, Philipp Albrecht, Lars Wojtecki, Sven G. Meuth, David Kremer

PMC · DOI: 10.3390/ijms26073412 · 2025-04-05

## TL;DR

This paper explores whether nitrosative stress molecules could be useful as biomarkers for tracking and understanding multiple sclerosis.

## Contribution

The paper proposes nitrosative stress markers as potential new biomarkers for multiple sclerosis.

## Key findings

- Neurofilament light chain (NfL) shows variability, limiting its clinical use.
- Combining NfL with glial fibrillary acidic protein (GFAP) improves specificity for MS progression.
- Nitrosative stress molecules like nitrate, nitrite, and 3NT are suggested as promising additional biomarkers.

## Abstract

Multiple sclerosis (MS), an auto-immune disease of the central nervous system (CNS) with inflammatory and neurodegenerative properties, remains an insufficiently understood disease despite more than 150 years of research. In contrast to diseases from other medical fields such as, for instance, oncology, a description of its clinical and non-clinical features based on readouts such as biomarkers is still in its infancy. While, in this regard, neurofilament light chain (NfL) seems to be a promising new tool, the significant intra- and interindividual variation of this serological marker somewhat limits its widespread applicability in everyday clinical reality. This has sparked novel studies in which glial fibrillary acidic protein (GFAP) was proposed as an on-top marker serving to improve overall specificity. In this context, it was found that MS disease progression was significantly more often associated with increased levels of both NfL and GFAP compared to increased NfL levels alone. This highlights the complexity of the disease while also emphasizing the potential benefits of introducing additional markers to enhance current options. We propose that nitrosative stress markers, such as nitrate, nitrite, and nitrotyrosine (3NT), could serve this purpose effectively.

## Linked entities

- **Proteins:** NEFL (neurofilament light chain), GFAP (glial fibrillary acidic protein)
- **Chemicals:** nitrate (PubChem CID 943), nitrite (PubChem CID 946)
- **Diseases:** multiple sclerosis (MONDO:0005301), MS (MONDO:0006861)

## Full-text entities

- **Genes:** NEFL (neurofilament light chain) [NCBI Gene 4747] {aka CMT1F, CMT2E, CMTDIG, NF-L, NF68, NFL}, GFAP (glial fibrillary acidic protein) [NCBI Gene 2670] {aka ALXDRD}
- **Diseases:** immune disease (MESH:D007154), MS (MESH:D009103), inflammatory (MESH:D007249)
- **Chemicals:** nitrate (MESH:D009566), nitrite (MESH:D009573), 3NT (MESH:C002744)

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Source: https://tomesphere.com/paper/PMC11989761