Kour Avneet, Dube Taru, Kumar Ashwani, Panda Jiban Jyoti
Institute of Nano Science and Technology, Mohali, Punjab 140306, India.
University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India.
Bioconjug Chem. 2022 Feb 16;33(2):397-410. doi: 10.1021/acs.bioconjchem.2c00007. Epub 2022 Feb 4.
The phenomenon of proteins/peptide assembly into amyloid fibrils is associated with various neurodegenerative and age-related human disorders. Inhibition of the aggregation behavior of amyloidogenic peptides/proteins or disruption of the pre-formed aggregates is a viable therapeutic option to control the progression of various protein aggregation-related disorders such as Alzheimer's disease (AD). In the current work, we investigated both the amyloid inhibition and disaggregation proclivity of levodopa-functionalized gold nanoroses (GNRs) against various peptide-based amyloid models, including the amyloid beta peptide [Aβ (1-42) and Aβ (1-40)] and the dipeptide phenylalanine-phenylalanine (FF). Our results depicted the anti-aggregation behavior of the GNR toward FF and both forms of Aβ-derived fibrils. The peptides demonstrated a variation in their fiber-like morphology and a decline in thioflavin T fluorescence after being co-incubated with the GNR. We further demonstrated the neuroprotective effects of the GNR in neuroblastoma cells against FF and Aβ (1-42) fiber-induced toxicity, exemplified both in terms of regaining cellular viability and reducing production of reactive oxygen species. Overall, these findings support the potency of the GNR as a promising platform for combating AD.
蛋白质/肽组装成淀粉样纤维的现象与各种神经退行性疾病和与年龄相关的人类疾病有关。抑制淀粉样肽/蛋白质的聚集行为或破坏预先形成的聚集体是控制各种与蛋白质聚集相关疾病（如阿尔茨海默病（AD））进展的可行治疗选择。在当前的工作中，我们研究了左旋多巴功能化的金纳米棒（GNRs）对各种基于肽的淀粉样模型的淀粉样抑制和解聚倾向，包括淀粉样β肽[Aβ(1 - 42)和Aβ(1 - 40)]和二肽苯丙氨酸 - 苯丙氨酸（FF）。我们的结果描述了GNR对FF以及两种形式的Aβ衍生纤维的抗聚集行为。与GNR共同孵育后，这些肽在纤维状形态上表现出变化，硫黄素T荧光下降。我们进一步证明了GNR在神经母细胞瘤细胞中对FF和Aβ(1 - 42)纤维诱导的毒性具有神经保护作用，这在恢复细胞活力和减少活性氧产生方面都得到了体现。总体而言，这些发现支持了GNR作为对抗AD的有前景平台的潜力。
