Modified TPP-MoS2 QD Blend as a Bio-Functional Model for Normalizing Microglial Dysfunction in Alzheimer's Disease

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease of old age. Accumulation of beta-amyloid peptide (A beta) and mitochondrial dysfunction results in chronic microglial activation, which enhances neuroinflammation and promotes neurodegeneration. Microglia are resident macrophages of the brain and spinal cord which play an important role in maintaining brain homeostasis through a variety of phenotypes, including the pro-inflammatory phenotype and anti-inflammatory phenotypes. However, persistently activated microglial cells generate reactive species and neurotoxic mediators. Therefore, inhibitors of microglial activation are seen to have promise in AD control. The modified TPP/MoS2 QD blend is a mitochondrion-targeted nanomaterial that exhibits cytoprotective activities and antioxidant properties through scavenging free radicals. In the present study, the cell viability and cytotoxicity of the DSPE-PEG-TPP/MoS2 QD blend on microglial cells stimulated by A beta were investigated. The levels of reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were also assessed. In addition, pro-inflammatory and anti-inflammatory cytokines, such as tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-1 beta (IL-1 beta), transforming growth factor beta (TGF-beta), inducible nitric oxide synthase (iNOS) and arginase-1 (Arg-I) were measured in the presence or absence of the DSPE-PEG-TPP/MoS2 QD blend on an immortalized microglia cells activated by accumulation of A beta. We found that the DSPE-PEG-TPP/MoS2 QD blend was biocompatible and nontoxic at specific concentrations. Furthermore, the modified TPP/MoS2 QD blend significantly reduced the release of free radicals and improved the mitochondrial function through the upregulation of MMP in a dose-dependent manner on microglial cells treated with A beta. In addition, pre-treatment of microglia with the DSPE-PEG-TPP/MoS2 QD blend at concentrations of 25 and 50 mu g/mL prior to A beta stimulation significantly inhibited the release and expression of pro-inflammatory cytokines, such as IL-1 beta, IL-6, TNF-alpha, and iNOS. Nevertheless, the anti-inflammatory cytokines TGF-beta and Arg-I were activated. These findings suggest that the modified TPP/MoS2 QD blend reduced oxidative stress, inflammation and improved the mitochondrial function in the immortalized microglial cells (IMG) activated by A beta. Overall, our research shows that the DSPE-PEG-TPP/MoS2 QD blend has therapeutic promise for managing AD and can impact microglia polarization.

Automated summary

Alzheimer's disease is a common neurodegenerative disease in old age, involving the accumulation of beta-amyloid peptide and mitochondrial dysfunction. This study investigates the potential of a modified TPP/MoS2 QD blend in managing Alzheimer's disease through protecting microglial cells and reducing inflammation. The results demonstrate that the blend has a beneficial impact on cell viability, oxidative stress, mitochondrial function, and cytokine expression in microglial cells stimulated by beta-amyloid peptide.