期刊
ACS NANO
卷 5, 期 7, 页码 6001-6007出版社
AMER CHEMICAL SOC
DOI: 10.1021/nn201773x
关键词
amyloidogenic peptide; peptide aggregation; modulation; neuronal cytotoxicity; chaperone-like molecules
类别
资金
- National Basic Research Program of China [2009CB930100]
- Chinese Academy of Sciences [KJCX2-YW-M15]
- National Natural Science Foundation of China [20911130229]
- CAS Key Laboratory for Biological Effects of Nanomaterials Nano-safety
The pathogenesis of many neurodegenerative diseases is associated with different types of aggregates of amyloidogenic peptides, including senile plaques, fibrils, protofibrils, and oligomers. It is therefore valuable to explore diversity of approaches toward reducing the cytotoxicity of amyloidogenic peptides by modulating aggregation behaviors. Herein we report an approach toward reducing the neuronal cytotoxicity of amyloidogenic peptides by accelerating the aggregation process, which Is different from prevalent methods via inhibiting the aggregation of peptides. The pyridyl derivatives behave like chaperones to dramatically change the assembling characteristics of the peptides via strong hydrogen bond formation with C-termini of amyloid beta (A beta) peptides, which is revealed by using scanning probe microscopy. The light scattering experiments demonstrated the effect of the chaperone-like molecules on accelerating the aggregation process of A beta peptides, accompanied by the reduced neuronal cytotoxicity of amyloidogenic peptides. These results would give rise to a complementary approach for modulating biological effects of the aggregates of amyloidogenic peptides.
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