Neurodegeneration in conditions like Alzheimer's and Parkinson's disease is influenced by genetic and environmental factors. This study explores the potential neurodegenerative effects of lead (Pb) toxicity and amyloid beta peptides (Aβp 1–40 and Aβp 25–35) by promoting M1 polarization in microglial cells. To this end, we investigated and observed that IC50 concentrations of Pb (22.8 μM) and Aβp 25–35(29.6 μM). Our results demonstrated significant Pb uptake (31.13% at 25 μM Pb) and increased intracellular ROS levels (77.1%) upon treatment with Pb in combination of both Aβp 1–40 and Aβp 25–35. Protein carbonylation significantly increased (73.12 nmol/mL) upon treatment with Pb in combination of both Aβp 1–40 and Aβp 25–35, indicating oxidative damage and compromised cellular defenses against oxidative stress along with elevated DNA oxidative damage (164.9 pg/mL of 8‐OH‐dG) upon treatment with Pb in combination with both Aβp 1–40 and Aβp 25–35. Microglial polarization showed elevated M1 markers (inducible nitric oxide synthase and cyclooxygenase 2) and reduced M2 markers (arginase‐1 and cluster of differentiation 206), suggesting Pb's role in inducing neurodegenerative microglial polarization. These findings provide insights into the complex molecular events contributing to Pb‐induced neurotoxicity and neurodegenerative diseases.

中文翻译：

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小胶质细胞中铅和淀粉样肽诱导 M1 极化：对神经变性过程的影响

阿尔茨海默病和帕金森病等疾病的神经退行性疾病受到遗传和环境因素的影响。本研究探讨了铅 (Pb) 毒性和淀粉样 β 肽（Aβp 1-40 和 Aβp 25-35）通过促进小胶质细胞 M1 极化而产生的潜在神经退行性影响。为此，我们研究并观察到 ​​Pb (22.8 μM) 和 Aβp 25–35 (29.6 μM) 的 IC50 浓度。我们的结果表明，结合 Aβp 1-40 和 Aβp 25-35 进行 Pb 处理后，Pb 吸收显着（25 μM Pb 时为 31.13%），细胞内 ROS 水平增加（77.1%）。用 Pb 联合 Aβp 1-40 和 Aβp 25-35 处理后，蛋白质羰基化显着增加 (73.12 nmol/mL)，表明氧化损伤和细胞对氧化应激的防御受损，同时 DNA 氧化损伤升高（164.9 pg/mL 8-OH-dG) 与 Pb 与 Aβp 1-40 和 Aβp 25-35 组合治疗后。小胶质细胞极化显示 M1 标记物（诱导型一氧化氮合酶和环氧合酶 2）升高，M2 标记物（精氨酸酶-1 和分化簇 206）减少，表明铅在诱导神经退行性小胶质细胞极化中的作用。这些发现为了解铅诱导的神经毒性和神经退行性疾病的复杂分子事件提供了见解。