首页> 外文期刊>RSC Advances >Gallic acid loaded onto polyethylenimine-coated human serum albumin nanoparticles (PEI-HSA-GA NPs) stabilizes α-synuclein in the unfolded conformation and inhibits aggregation
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Gallic acid loaded onto polyethylenimine-coated human serum albumin nanoparticles (PEI-HSA-GA NPs) stabilizes α-synuclein in the unfolded conformation and inhibits aggregation

机译:加载到聚乙基菊醋胺涂覆的人血清白蛋白纳米颗粒(PEI-HSA-GA NPS)上的Gallic酸稳定在展开的构象中稳定α-突触核蛋白并抑制聚集

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The aggregation of the 140-residue protein α-synuclein (αSN) plays a major role in the pathogenesis of different neurodegenerative disorders such as Parkinson's Disease (PD). Previous reports indicated that the antioxidant gallic acid (GA) can inhibit αSN aggregation. As the transport of GA to the brain due to the lipophilic nature of endothelial cells is prevented, we loaded GA onto positively charged polyethylenimine-coated human serum albumin (PEI-HSA) NPs and investigated the properties of these nanoparticles as drug carriers. Using an array of different techniques, we determined that GA on GA loaded PEI-HSA NPs (PEI-HSA-GA NPs) decreases the interaction of the NPs with αSN and stabilizes αSN in the unfolded conformation. These interactions lead to different effects on the αSN aggregation. While the rate of αSN aggregation increased in the presence of PEI-HSA NPs and free GA (PEI-HSA NPs + GA) due to the effect of PEI-HSA NPs, PEI-HSA-GA NPs inhibited αSN aggregation to the same extent as free GA in a concentration dependent manner. Additionally, GA inhibited the interaction of PEI-HSA-GA NPs with calcein filled vesicles, in accordance with our previous study indicating that loading GA can decrease the toxicity of PEI-HSA NPs. Also, PEI-HSA NPs not only inhibited αSN oligomers' perturbation of the membrane but also decreased the level of toxic oligomers. We conclude from our data that PEI-HSA-GA NPs are promising candidates for efficient delivery of GA to the brain.
机译:140-残基蛋白α-突触核蛋白(αSn)的聚集在不同神经变性障碍的发病机制中起主要作用,例如帕金森病(Pd)。以前的报道表明抗氧化神经酸(Ga)可以抑制αsn聚集。由于防止了由于内皮细胞的亲脂性质而导致GRe的传输,我们将Ga加载到带正电荷的聚乙胺涂覆的人血清白蛋白(PEI-HSA)NPS上,并研究了这些纳米颗粒的性质作为药物载体。使用不同技术的阵列,我们确定GA在GA加载的PEI-HSA NPS(PEI-HSA-GA NPS)上降低了NPS与αSN的相互作用并稳定αSN在展开的构象中。这些相互作用导致对αsn聚合的不同影响。虽然由于PEI-HSA NPS的效果,PEI-HSA-GA NPS抑制了与相同程度的αsn聚集在相同以浓度依赖方式自由Ga。另外,根据我们以前的研究表明,根据我们以前的研究,GA抑制了PEI-HSA-GA NP与Calcein填充囊泡的相互作用,所述研究表明Laboud Ga可以降低Pei-HSA NP的毒性。此外,PEI-HSA NPS不仅抑制αSN低聚物的膜的扰动,还降低了有毒低聚物的水平。我们从我们的数据中得出结论,即PEI-HSA-GA NPS承诺候选人,以便高效地向大脑提供GA。

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