期刊
PEPTIDES
卷 27, 期 11, 页码 2858-2866出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.peptides.2006.04.022
关键词
beta-amyloid aggregation; Alzheimer's disease; DSPE-PEG(2000); PEGylated phospholipid; nanomicelles; SHSY-5Y cells; nanomedicine
资金
- NCRR NIH HHS [C06 RR15482] Funding Source: Medline
- NHLBI NIH HHS [R01 HL72323] Funding Source: Medline
- NIA NIH HHS [R01 AG024026] Funding Source: Medline
beta-Amyloid (A beta) is a hydrophobic peptide that drives the pathogenesis of Alzheimer's disease (AD) due to its aberrant aggregation. Inhibition of A beta 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 A beta-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. alpha-Helicity of A beta-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 A beta-42 (p < 0.05). Collectively, our results establish that PEGylated phospholipids abrogate transformation of A beta-42 to amyloidogenic beta-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. (c) 2006 Elsevier Inc. All rights reserved.
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