title: Observation of reduced cytotoxicity of aggregated amyloidogenic peptides with chaperone-like molecules.
abstract: 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 β (Aβ) 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 Aβ 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.
authors.affiliation: National Center for Nanoscience and Technology, Beijing 100190, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.forename: Lan
authors.initials: L
authors.lastname: Zhang
authors.forename: Lin
authors.initials: L
authors.lastname: Niu
authors.forename: Meng
authors.initials: M
authors.lastname: Xu
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Mao
authors.forename: Yanlian
authors.initials: Y
authors.lastname: Yang
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000633:toxicity*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D011725:Pyridines / Q000737:chemistry; D012996:Solutions
chemical_list: D016229:Amyloid beta-Peptides; D011725:Pyridines; D012996:Solutions; C023666:pyridine