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

Area of Science:

• Neuroscience
• Biomaterials Science
• Pharmacology

Background:

• Alzheimer's disease (AD) involves β-amyloid peptide (Aβ) accumulation, leading to chronic microglial activation, neuroinflammation, and neurodegeneration.
• Microglia, the brain's resident immune cells, can become persistently activated, producing harmful reactive species and neurotoxic mediators.
• Inhibiting microglial activation is a promising strategy for AD treatment.

Purpose of the Study:

• To investigate the therapeutic potential of a modified TPP/MoS2 QD blend (DSPE-PEG-TPP/MoS2 QD) in an Alzheimer's disease model.
• To assess the effects of the DSPE-PEG-TPP/MoS2 QD blend on microglial cell viability, cytotoxicity, reactive oxygen species (ROS) levels, and mitochondrial membrane potential (MMP).
• To evaluate the impact of the DSPE-PEG-TPP/MoS2 QD blend on pro-inflammatory and anti-inflammatory cytokine expression in Aβ-stimulated microglial cells.

Main Methods:

• Cultured immortalized microglial cells were stimulated with β-amyloid peptide (Aβ) to mimic AD conditions.
• The cytocompatibility and cytotoxicity of the DSPE-PEG-TPP/MoS2 QD blend were evaluated.
• Levels of reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were measured.
• Pro-inflammatory (TNF-α, IL-6, IL-1β, iNOS) and anti-inflammatory (TGF-β, Arg-I) cytokines were quantified using the DSPE-PEG-TPP/MoS2 QD blend.

Main Results:

• The DSPE-PEG-TPP/MoS2 QD blend demonstrated biocompatibility and non-toxicity at specific concentrations.
• The blend significantly reduced free radical release and enhanced mitochondrial function by upregulating MMP in Aβ-treated microglial cells, in a dose-dependent manner.
• Pre-treatment with the DSPE-PEG-TPP/MoS2 QD blend suppressed pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, iNOS) while promoting anti-inflammatory cytokines (TGF-β, Arg-I).

Conclusions:

• The DSPE-PEG-TPP/MoS2 QD blend effectively mitigates oxidative stress and neuroinflammation in Aβ-activated microglial cells.
• This nanomaterial improves mitochondrial function, suggesting a potential therapeutic strategy for Alzheimer's disease.
• The DSPE-PEG-TPP/MoS2 QD blend influences microglial polarization, offering promise for AD management.