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Investigating the role of ras-related c3 botulinum toxin substrate 1(rac1) in modulating tumor necrosis factor alpha (tnf-α) mediated inflammation in a streptozotocin-induced mouse model of Alzheimer's disease

Bakhshnda Omar
Department of Clinical Biochemistry, College of Health Sciences, Hawler Medical University, Erbil, Kurdistan Reign, Iraq.
Rundk Hwaiz
Department of Nutrition and Dietetics, College of Health Sciences, Hawler Medical University, Erbil, Kurdistan Reign, Iraq.
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Copyright (c) 2025 Bakhshnda Omar, Rundk Hwaiz (Author)

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Abstract

Background and objective: Alzheimer's disease (AD) is a slowly worsening brain disease linked to ongoing inflammation, with Tumor Necrosis Factor Alpha (TNF-α) playing a significant function in its progression. Ras-related C3 botulinum toxin Substrate 1(Rac1)regulates inflammatory signaling and may influence TNF-α expression in AD. The aim is to investigate the impacts of Rac1 inhibition on TNF-α expression and neuropathology in a streptozotocin (STZ)-induced AD mouse model.

Methods: There were three groups of male Swiss albino mice: Control (control), STZ (AD model), and NSC23366 + STZ (Rac1 inhibitor). The treatment group received 5 mg/kg NSC23366 before STZ administration. ELISA measured TNF-α, amyloid beta 42 (Aβ42) and tau levels in the brain and serum. Histopathological analysis assessed neuroinflammation and neuronal damage.

Results: Streptozotocin (STZ) significantly increased Aβ42, tau, and TNF-α levels (P <0.05). NSC23366 treatment reduced these markers, indicating neuroprotection. In the STZ group, histological analysis showed severe neuroinflammation and neuronal damage. Conversely, NSC23366 reduced the quantity of inflammatory cells and scores of brain injury (P <0.05).

Conclusion: Blocking Rac1 lowers neuroinflammation caused by TNF-α, lowers the damage caused by tau and amyloid plaques, and slows down neurodegeneration in AD. Targeting Rac1 may provide an achievable therapeutic strategy for the management of Alzheimer's condition.

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How to Cite
Omar, B. ., & Hwaiz, R. . (2025). Investigating the role of ras-related c3 botulinum toxin substrate 1(rac1) in modulating tumor necrosis factor alpha (tnf-α) mediated inflammation in a streptozotocin-induced mouse model of Alzheimer’s disease. Zanco Journal of Medical Sciences (Zanco J Med Sci), 29(3), 671–678. https://doi.org/10.15218/zjms.2025.072

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