Significance of native PLGA nanoparticles in the treatment of Alzheimer’s disease pathology  

作　　者：Bibin Anand Qi Wu Maryam Nakhaei-Nejad Govindarajan Karthivashan Lyudmyla Dorosh Sara Amidian Abhishek Dahal Xiuju Li Maria Stepanova Holger Wille Fabrizio Giuliani Satyabrata Kar 

机构地区：[1]Department of Medicine(Neurology),University of Alberta,Edmonton,Alberta,T6G 2M8,Canada [2]Centre for Prions and Protein Folding Diseases,University of Alberta,Edmonton,Alberta,T6G 2M8,Canada [3]Department of Electrical and Computer Engineering,University of Alberta,Edmonton,Alberta,T6G 2M8,Canada [4]Department of Biochemistry,University of Alberta,Edmonton,Alberta,T6G 2M8,Canada [5]Neuroscience and Mental Health Institute,University of Alberta,Edmonton,Alberta,T6G 2M8,Canada

出　　处：《Bioactive Materials》2022年第11期506-525,共20页生物活性材料（英文）

摘　　要：Alzheimer’s disease (AD) is believed to be triggered by increased levels/aggregation of β-amyloid (Aβ) peptides. At present, there is no effective disease-modifying treatment for AD. Here, we evaluated the therapeutic potential of FDA-approved native poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles on Aβ aggregation and in cellular/ animal models of AD. Our results showed that native PLGA can not only suppress the spontaneous aggregation but can also trigger disassembly of preformed Aβ aggregates. Spectroscopic studies, molecular dynamics simu-lations and biochemical analyses revealed that PLGA, by interacting with the hydrophobic domain of Aβ1-42, prevents a conformational shift towards the β-sheet structure, thus precluding the formation and/or triggering disassembly of Aβ aggregates. PLGA-treated Aβ samples can enhance neuronal viability by reducing phosphor-ylation of tau protein and its associated signaling mechanisms. Administration of PLGA can interact with Aβ aggregates and attenuate memory deficits as well as Aβ levels/deposits in the 5xFAD mouse model of AD. PLGA can also protect iPSC-derived neurons from AD patients against Aβ toxicity by decreasing tau phosphorylation. These findings provide unambiguous evidence that native PLGA, by targeting different facets of the Aβ axis, can have beneficial effects in mouse neurons/animal models as well as on iPSC-derived AD neurons - thus signifying its unique therapeutic potential in the treatment of AD pathology.

关 键 词：Alzheimer’s disease Β-AMYLOID Nanoparticles NEUROPROTECTION Peptide aggregation 

分 类 号：R318[医药卫生—生物医学工程] R74[医药卫生—基础医学]