Yadav Yudhishthir, Anwar Masroor, Sharma Hanuman, Jain Suman, Sharma Uma, Haldar Partha, Dey Aparajit B, Dey Sharmistha
Department of Biophysics, All India Institute of Medical Sciences, New Delhi 110029, India.
Bioanalytics Facility, All India Institute of Medical Sciences, New Delhi 110029, India.
Cells. 2025 Jun 23;14(13):957. doi: 10.3390/cells14130957.
Neuroinflammation, triggered by lipoxygenase (LOX), contributes to Alzheimer's disease (AD) progression. Overexpression of LOX-5 in patients with AD serum highlights its role. This study assessed the efficacy of the LOX-inhibitor-peptide YWCS in an AD rat model induced by Aβ injection. Cognitive tests, magnetic resonance imaging (MRI) scans, and molecular analyses were conducted. YWCS treatment significantly improved cognitive function, as evidenced by improved performance in the open field, novel object recognition, elevated plus maze, and Morris water maze tests. MRI scans revealed hippocampal shrinkage in AD rats and no changes were observed from YWCS treatment. Molecular analysis revealed altered expression of LOX-5, LOX-12, Aβ, γ-secretase components, p-Tau, Akt, p-Akt, and p53 in AD rats. Immunofluorescence staining confirmed increased expression of LOX, Aβ, and p-Tau in the hippocampus of AD rats, which was reduced by YWCS treatment. Serum LOX levels were elevated in AD rats and significantly decreased after YWCS treatment, aligning with previous findings in human AD patients and AD cell models. YWCS offered improvements in behavioral and inflammatory marker regulation and also prevented progression of the disease, as shown by MRI results. These results suggest that YWCS, by targeting LOX, has the potential to be a promising therapeutic agent for AD.
由脂氧合酶（LOX）引发的神经炎症会促进阿尔茨海默病（AD）的进展。AD患者血清中LOX-5的过表达凸显了其作用。本研究评估了LOX抑制剂肽YWCS在Aβ注射诱导的AD大鼠模型中的疗效。进行了认知测试、磁共振成像（MRI）扫描和分子分析。YWCS治疗显著改善了认知功能，在旷场试验、新物体识别试验、高架十字迷宫试验和莫里斯水迷宫试验中的表现改善证明了这一点。MRI扫描显示AD大鼠海马萎缩，而YWCS治疗未观察到变化。分子分析显示AD大鼠中LOX-5、LOX-12、Aβ、γ-分泌酶成分、p- Tau、Akt、p-Akt和p53的表达发生改变。免疫荧光染色证实AD大鼠海马中LOX、Aβ和p-Tau的表达增加，而YWCS治疗使其减少。AD大鼠血清LOX水平升高，YWCS治疗后显著降低，这与之前在人类AD患者和AD细胞模型中的发现一致。如MRI结果所示，YWCS改善了行为和炎症标志物调节，还预防了疾病进展。这些结果表明，YWCS通过靶向LOX，有可能成为一种有前景的AD治疗药物。
