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Ras Homolog Family Member A Regulates Interleukin-6 Expression in Streptozotocin-Pretreated Mice with Relevance to Alzheimer’s Disease-Related Inflammation

Kanyaw Abdulrahman
Department of Clinical Biochemistry, College of Health Sciences, Hawler Medical University, Erbil, Kurdistan Region, Iraq.
Rundk Hwaiz
Department of Nutrition and Dietetics, College of Health Sciences, Hawler Medical University, Erbil, Kurdistan Region, Iraq.
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Copyright (c) 2026 Kanyaw Abdulrahman, Rundk Hwaiz (Author)

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Abstract

Background and objective: Alzheimer's disease (AD) is a slowly worsening brain disorder linked to ongoing inflammation, with interleukin-6 (IL-6) playing a significant role in its progression. Ras Homolog Family Member A (RhoA) regulates inflammatory signaling and may influence IL-6 expression in AD. This research aimed to investigate the impact of RhoA inhibition on IL-6 expression and neuropathology in a streptozotocin (STZ)-induced AD mouse model.

Methods: A total of 15 male Swiss albino mice, aged 8–9 weeks and weighing 25–30 g, were randomly assigned into three groups (n = 5 per group): Control (control), STZ-pretreated (diabetes-associated cognitive impairment like Alzheimer’s diseasemodel), and Y-27632+STZ (RhoA inhibitor-treated). The treatment group received 5 mg/kg Y-27632 before STZ administration. ELISA measured IL-6, amyloid beta 42 (Aβ42), and tau levels in brain and serum. Histopathological analysis assessed neuroinflammation and neuronal damage.

Results: STZ significantly increased Aβ42, tau, and IL-6 levels (P <0.05). Y-27632 treatment reduced these markers, indicating neuroprotection. Histological analysis revealed severe neuroinflammation and neuronal damage in the STZ group, while Y-27632 reduced inflammatory cell infiltration and brain injury scores (P <0.05).

Conclusion: RhoA inhibition attenuates IL-6-mediated neuroinflammation, decreases tau and amyloid plaque pathology, and mitigates neurodegeneration in AD. Targeting RhoA may offer a promising therapeutic approach for AD management.

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How to Cite
Abdulrahman, K., & Hwaiz , R. . (2026). Ras Homolog Family Member A Regulates Interleukin-6 Expression in Streptozotocin-Pretreated Mice with Relevance to Alzheimer’s Disease-Related Inflammation. Zanco Journal of Medical Sciences (ZJMS), 30(2), 483–497. https://doi.org/10.15218/zjms.2026.033

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