Dual Effect of Prussian Blue Nanoparticles on Aβ40 Aggregation: β-Sheet Fibril Reduction and Copper Dyshomeostasis Regulation

Abstract

Alzheimer's disease (AD), affecting almost 50 million individuals worldwide, is currently the first cause of dementia. Despite the tremendous research efforts in the last decade, only four supportive or palliative drugs, namely, acetylcholinesterase (AChE) inhibitors donepezil, galantamine, and rivastigmine and the glutamate NMDA receptor antagonist memantine, are currently available. New therapeutic strategies are becoming prominent, such as the direct inhibition of amyloid formation or the regulation of metal homeostasis. In the present report, the potential use of Prussian blue (PB), a drug that is in the World Health Organization Model List of Essential Medicines, in AD treatment is demonstrated. Both in vitro and in cellulo studies indeed suggest that PB nanoparticles (PBNPs) are capable of reducing the formation of typical amyloid-β fibers (detected by thioflavin T fluorescence) and restoring the usual amyloid fibrillation pathway via chelation/sequestration of copper, which is found in high concentrations in senile plaques.

New Pyrimidine and Pyridine Derivatives as Multitarget Cholinesterase Inhibitors: Design, Synthesis, and In Vitro and In Cellulo Evaluation

“…coli. However, the low anti-amyloid activity reported could also be due to an unusually low ability of the compounds to cross the bacterial wall. Although it is unusual, this effect has been observed recently and should not be ruled out …”

“…Although it is unusual, this effect has been observed recently and should not be ruled out. 41 In conclusion, this research has allowed one to identify interesting lead compounds for the development of new multifunctional molecules useful for AD by virtue of their inhibitory activity toward ChEs, as well as for chelating and antioxidant abilities, low toxicity, and good predicted ADME parameters.…”

Methylene Blue-Doped Carbonized Polymer Dots: A Potent Photooxygenation Scavenger Targeting Alzheimer’s β-Amyloid

“…Therefore, it is unreasonable to monitor Aβ aggregation by ThT dye. It has been demonstrated that CR can specifically bind to the hydrophobic region of amyloid fibrils and exhibit enhanced absorption at 540 nm . Therefore, the CR probe was used to detect the inhibitory potency of MB-CPDs.…”

Nanomaterials for Modulating the Aggregation of β-Amyloid Peptides

“…According to the previous reports, it can act as a nanozyme to scavenge ROS and trap metal ions in its lattice cavities. Recently, Kowalczyk et al studied the dual effects of PB on inhibiting Aβ 1–40 aggregation and chelating Cu 2+ [ 163 ]. They found that PBcould accelerate the nucleation of Aβ 1–40 and facilitate the formation of Aβ 1–40 amorphous aggregates instead of β-sheet fibrils.…”