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Purpose <p>This study focuses on the evaluation of the therapeutic potential of Tetrascorpin-1 (AaTs-1), a tetrapeptide isolated from <i>Androctonus australis hector</i> venom, proposed as a putative formyl peptide receptor 2 (FPR2) antagonist, in a cuprizone-induced murine model of Multiple sclerosis (MS), a chronic autoimmune and inflammatory disease of the central nervous system.</p> Methods <p>Acute demyelination was induced in mice by administering cuprizone (0.2% w/w in the diet) for six weeks. During the sixth week of cuprizone intake, demyelinated mice received intranasal administration of AaTs-1 at a dose of 50–100&#xa0;µg/kg for five consecutive days, with 24-hour intervals between treatments.</p> Results <p>Behavioral assessments, immunological assays, and histological analyses revealed that AaTs-1 improved body weight, reduced behavioral impairments and mitigated neuroinflammation by suppressing astrogliosis and microgliosis, lowering myeloperoxidase (MPO) and nuclear factor kappa B (NF-κB) levels, and downregulating proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), while upregulating the anti-inflammatory cytokine interleukin-10 (IL-10) in serum. Moreover, AaTs-1 restored oxidative balance by reducing nitric oxide (NO), hydrogen peroxide (H₂O₂), and malondialdehyde (MDA) levels and enhancing catalase activity and glutathione (GSH) levels.</p> Conclusion <p>Overall, our findings indicate that AaTs-1 confers significant neuroprotective effects by limiting neuroinflammation and oxidative stress, thereby enhancing remyelination and functional recovery.</p>

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AaTs-1, a Tetrapeptide from Scorpion Venom Mitigates Demyelination and Neuroinflammation in a Cuprizone-Induced Model of Multiple Sclerosis

  • 期刊论文

  • 发表日期：

    2026年6月20日

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  • Hadjila Moussaoui,
  • Meriem Amarni,
  • Amina Ladjel-Mendil,
  • Mohamed-Chiheb Saada,
  • Wassim Moslah,
  • Merzouagui Rania,
  • Najet Srairi-Abid,
  • Fatima Laraba-Djebari

摘要

Purpose

This study focuses on the evaluation of the therapeutic potential of Tetrascorpin-1 (AaTs-1), a tetrapeptide isolated from Androctonus australis hector venom, proposed as a putative formyl peptide receptor 2 (FPR2) antagonist, in a cuprizone-induced murine model of Multiple sclerosis (MS), a chronic autoimmune and inflammatory disease of the central nervous system.

Methods

Acute demyelination was induced in mice by administering cuprizone (0.2% w/w in the diet) for six weeks. During the sixth week of cuprizone intake, demyelinated mice received intranasal administration of AaTs-1 at a dose of 50–100 µg/kg for five consecutive days, with 24-hour intervals between treatments.

Results

Behavioral assessments, immunological assays, and histological analyses revealed that AaTs-1 improved body weight, reduced behavioral impairments and mitigated neuroinflammation by suppressing astrogliosis and microgliosis, lowering myeloperoxidase (MPO) and nuclear factor kappa B (NF-κB) levels, and downregulating proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), while upregulating the anti-inflammatory cytokine interleukin-10 (IL-10) in serum. Moreover, AaTs-1 restored oxidative balance by reducing nitric oxide (NO), hydrogen peroxide (H₂O₂), and malondialdehyde (MDA) levels and enhancing catalase activity and glutathione (GSH) levels.

Conclusion

Overall, our findings indicate that AaTs-1 confers significant neuroprotective effects by limiting neuroinflammation and oxidative stress, thereby enhancing remyelination and functional recovery.