PEGylated phospholipid nanomicelles interact with β-amyloid (1–42) and mitigate its β-sheet formation, aggregation and neurotoxicity in vitro

Abstract

β-Amyloid (Aβ) is a hydrophobic peptide that drives the pathogenesis of Alzheimer's disease (AD) due to its aberrant aggregation. Inhibition of Aβ aggregation process is one of the most promising strategies for therapeutic intervention in AD. Here, we demonstrate that sterically stabilized (PEGylated) phospholipid nanomicelles (SSM) are effective in mitigating Aβ-42 aggregation using several deterministic techniques such as (1) Turbidimetry (2) Congo red binding (3) Thioflavine-T binding (4) Laser light scattering and (5) Electron Microscopy. α-Helicity of Aβ-42 is significantly augmented in the presence of SSM as demonstrated by circular dichroism ( p < 0.05). Cytotoxicity studies, employing human neuroblastoma SHSY-5Y cells, established that PEGylated phospholipid associated peptide demonstrated significantly lower neurotoxicity compared to lipid untreated Aβ-42 ( p < 0.05). Collectively, our results establish that PEGylated phospholipids abrogate transformation of Aβ-42 to amyloidogenic β-sheeted form and impart neuroprotection in vitro. This study provides a foundation for designing nanoconstructs of PEGylated phospholipid nanomicelles in conjunction with a therapeutic agent for multitargeting the different pathophysiologies associated with AD.