Attenuation of the Aggregation and Neurotoxicity of Amyloid Peptides with Neurotransmitter-Functionalized Ultra-Small-Sized Gold Nanoparticles
Abstract
Alzheimers disease (AD) is closely associated with the self-aggregation of beta-amyloid peptides (Aβ). The neuron cytotoxicity of assembled Aβ fibrils has been extensively studied. In this work, ultra-small-sized gold nanoparticles (USGNPs, with diameter of ~4 nm) are synthesized and conjugated with neurotransmitter dopamine (DA) and its synthetic precursors (L-phenylalanine (L-Phe) and L-tyrosine (L-Tyr)). It is found that the fibrillation process of Aβ can be efficiently inhibited by these functionalized USGNPs, which is essentially ascribed to the screened growth points on the short seeds after being anchored by functionalized USGNPs as well as the disturbing of the peptide folding process in solution as revealed by the transmission electron microscope (TEM) and circular dichroism (CD) spectroscopic measurements. More interestingly, the neuron cells (PC12 as a model) exhibit noticeably improved viability (~90%) when treated with functionalized USGNPs in contrast to the control treated with Aβ growth solution alone (~70%). Because of the superior inhibition effect on the Aβ fibrillation as well as the remarkable cell protection effect, these functionalized USGNPs would afford insight information for the rational design of efficient strategy for AD treatment.
