The
abnormal aggregation of amyloid beta (Aβ or A beta) from
monomeric proteins into amyloid fibrils is an important pathological
contact to Alzheimer’s disease (AD). Amyloid beta 40 (Aβ40),
the pivotal biomarker of AD, aggregates to form amyloid plaques. For
this reason, inhibition of amyloid fibrillation had become a crucial
prevention and therapeutic strategy. Usually, LVFFA is the central
hydrophobic fragment of Aβ and can inhibit the aggregation of
Aβ40. In this work, in order to improve the inhibitory ability
of LVFFA, hexapeptide CLVFFA were conjugated at the surface of Au
clusters (AuNCs) to manufacture a nanosized inhibitor, AuNCs-CLVFFA.
Thioflavin T fluorescence and transmission electron microscope results
showed that AuNCs-CLVFFA inhibited Aβ40 fibrillogenesis, fibrils’
prolongation, and mature fibrils’ disaggregation. Furthermore,
AuNCs as the backbone of the inhibitor showed extraordinary inhibition
ability for Aβ40 aggregation at a low AuNCs-CLVFFA concentration.
Free hexapeptide CLVFFA, at the same concentration, showed almost
no inhibition. Additionally, the inhibitor could maintain the optical
properties of nanoclusters, and the cell viability demonstrated that
the inhibitor had good biocompatibility and may potentially be applied
into AD therapy or treatment.