# Progressive Elevation of Store-Operated Calcium Entry-Associated Regulatory Factor (SARAF) and Calcium Pathway Dysregulation in Multiple Sclerosis

**Authors:** Safa Taha, Muna Aljishi, Ameera Sultan, Moudi E. Al-Nashmi, Moiz Bakhiet, Salvatore Spicuglia, Mohamed Belhocine

PMC · DOI: 10.3390/ijms26104520 · International Journal of Molecular Sciences · 2025-05-09

## TL;DR

This study shows that calcium regulation proteins like SARAF are elevated in multiple sclerosis patients, suggesting a potential role in disease progression and treatment.

## Contribution

The study identifies progressive elevation of SARAF and altered calcium pathway proteins as potential biomarkers and therapeutic targets in MS.

## Key findings

- MS patients had significantly higher SARAF levels compared to healthy controls.
- STIM1 and ORAI1 expressions were significantly reduced in MS patients.
- Elevated intracellular calcium levels were observed in both early and late MS stages.

## Abstract

Multiple Sclerosis (MS) is a chronic autoimmune disorder characterized by demyelination and neuronal damage in the central nervous system. Dysregulation of calcium homeostasis, particularly through the Store-Operated Calcium Entry-Associated Regulatory Factor (SARAF), has been implicated in MS pathogenesis. This study investigated SARAF, STIM1, and Orai1 expression patterns and their relationship to calcium homeostasis in 45 Bahraini MS patients and 45 matched healthy controls using ELISA and real-time PCR analyses. MS patients showed significantly elevated serum SARAF levels in both early (192.26 ± 47.00 pg/mL) and late MS stages (341.47 ± 96.19 pg/mL) compared to controls (129.82 ± 30.82 pg/mL; p < 0.001. SARAF expressions were markedly increased in MS patients (3.829 ± 0.04422 vs. 1 ± 0; p < 0.0001), while STIM1 (0.4324 ± 0.01471) and ORAI1 (0.2963 ± 0.02156) expressions were significantly reduced compared to the controls (p < 0.0001). Intracellular calcium levels were notably elevated in both early and late MS stages. These findings suggest that the progressive elevation of SARAF, coupled with altered STIM1 and ORAI1 expression, may serve as potential biomarkers for MS progression and represent promising therapeutic targets.

## Linked entities

- **Genes:** SARAF (store-operated calcium entry associated regulatory factor) [NCBI Gene 51669], STIM1 (stromal interaction molecule 1) [NCBI Gene 6786], ORAI1 (ORAI calcium release-activated calcium modulator 1) [NCBI Gene 84876]
- **Diseases:** Multiple Sclerosis (MONDO:0005301)

## Full-text entities

- **Genes:** STIM1 (stromal interaction molecule 1) [NCBI Gene 6786] {aka D11S4896E, GOK, IMD10, STRMK, TAM, TAM1}, SARAF (store-operated calcium entry associated regulatory factor) [NCBI Gene 51669] {aka FOAP-7, HSPC035, TMEM66, XTP3}, ORAI1 (ORAI calcium release-activated calcium modulator 1) [NCBI Gene 84876] {aka CRACM1, IMD9, ORAT1, TAM2, TMEM142A}
- **Diseases:** neuronal damage (MESH:D009410), demyelination (MESH:D003711), MS (MESH:D009103), autoimmune disorder (MESH:D001327)
- **Chemicals:** Calcium (MESH:D002118)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12110777/full.md

## References

32 references — full list in the complete paper: https://tomesphere.com/paper/PMC12110777/full.md

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Source: https://tomesphere.com/paper/PMC12110777