M1 polarization induction by lead and amyloid peptides in microglial cells: Implications for neurodegeneration process

Abstract 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.