Thesis

Lysozyme-encapsulated gold nanoclusters as a potential therapy for Alzheimer’s disease

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Awarding institution
  • University of Strathclyde
Date of award
  • 2025
Thesis identifier
  • T17413
Person Identifier (Local)
  • 202266199
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Abstract
  • Background: Alzheimer's disease (AD), the most common cause of dementia, is characterisedby synaptic loss and neurodegeneration. Amyloid-? (A?) accumulation into plaques,hyperphosphorylation of tau protein, and neurofibrillary tangles (NFTs) in the brain areconsidered the pathological hallmarks of AD. However, more recent evidence suggests thatneuroinflammation plays a key role in the pathophysiology of AD and causes dysregulatedcellular activity and neurodegeneration by over-activating microglia. Novel lysozymeencapsulated gold nanoclusters have immunomodulatory roles like inhibiting the formation A?plaques via the modulation of immune responses mediated by microglial cells and can thereforebe used as a new therapy for AD.Hypothesis: Lysozyme-encapsulated gold nanoclusters (Lys-AuNCs) influence AD pathologythrough modulating immune responses mediated by microglial cells and hence may be used asa therapy for AD.Methodology: Lys-AuNCs were synthesised using a modified ‘one-pot process’ addingfiltration to account for sterile cell culture. Lys-AuNCs were characterised through fluorescentlifetime measurements with concentrations calculated from calibration curves to ensurephysiochemical and optical propertiesremained intact. Activation of microglial cell line HMC3by Lys-AuNCs was confirmed by positive staining with microglia marker IBA-1, thenmicroglial phenotype was investigated through cell morphological analysis via phase imaging.Toxicity of Lys-AuNCs on HMC3s was determined via MTT assay. Localisation of LysAuNCs were visualised via z-stack imaging of HMC3 cells. Pro- and anti-inflammatorymarkers iNOS and Arg-1 expression induced by Lys-AuNCs were assessed through stainingand quantified using ImageJ software.Results: HMC3 cells displayed resting morphology when treated with concentrations of LysAuNCs ranging from 50-600 ?g/mL with some cells displaying activated morphology at 200?g/mL. Lys-AuNCs induced a slight decrease in viability in HMC3 cells at 600 ?g/mL after72 hours (-88.9%;*p<0.05) compared to untreated cells, with no significant decrease inviability across other concentrations. HMC3 cells treated with 10 ?g/mL of Lys-AuNCsshowed an increase in iNOS expression with no significant changes seen in otherconcentrations (5, 50 and 200 ?g/mL) (**p<0.01). Treated cells showed a significant reduction in Arg-1 expression across all concentrations (5, 10, 50 and 200 ?g/mL) (****p<0.0001). Cellstreated with 50 and 200 ?g/mL of Lys-AuNCs showed intracellular localisation of clusters inHMC3 cells with staining and confocal imaging.Conclusions: Results showed that Lys-AuNCs induced minimal toxicity in HMC3 cellstreatedwith 600 ?g/ mL after 72 hours and no toxicity in all other concentrations. It can be confirmedthat Lys-AuNCs can activate and modulate the immune response of microglial cells withmorphology changes and marked pro-inflammatory mediator expression thus, targetingmicroglia should be further investigated as it may provide a potential effective therapy againstAD.
Advisor / supervisor
  • Jiang, Hui-Rong
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DOI

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