Feb 10, 2010
Can nanoparticles treat amyloid-related diseases?
Amyloid-related diseases represent more than 20 diseases, from Alzheimer's and Parkinson's diseases to type II diabetes, associated with the self-assembly of protein into amyloid aggregates. Although the clinical and biochemical characteristics are distinct, the amyloid aggregates – oligomers and fibrils – possess common structural characteristics described by a beta-sheet core structure. The pathogenesis of these diseases remains unclear despite intense multidisciplinary activity.
Results from various cell and animal models already suggest that a reduction of amyloid aggregation is beneficial. Now, researchers from IEP SAS in Kosice, Slovakia, and ISMN-CNR in Bologna, Italy, have investigated the effect of electrostatically stabilized magnetic nanoparticles (NPs) of Fe3O4 on the amyloid aggregation of lysozyme in vitro, as a prototypical amyloidogenic protein.
The work, published in the journal Nanotechnology, indicates that nanoparticles are able to inhibit the formation of amyloid aggregates and decrease the amount of amyloid fibrils. AFM images show amyloid fibrils of lysozyme (figure a) and their destruction after incubation with an increasing concentration of NPs (figures b and c). A spectroscopic technique was used to obtain IC50 and DC50 values, which indicate that NPs are able to decrease the amount of lysozyme aggregation already at stoichiometric concentrations. These features make NPs of potential interest as therapeutic agents against amyloid-related diseases.
The experimental data also provide other very interesting evidence; in vitro interaction of NPs with lysozyme does not promote amyloid aggregation. It is an important observation due to the fact that interaction of proteins with nanoparticles possessing a strong ability to promote protein amyloid aggregation can induce the onset or accelerate the development of amyloid disease.
This study proposes the potential therapeutic use of NPs in the prevention and treatment of amyloid-related diseases as well as their non-risk exploitation in nanomedicine and nanodiagnostics.
These findings will be employed for future investigation of the effect of various types of NPs on amyloid aggregates as the nanoparticle size, structure, surface composition and charge markedly influence their affect on amyloid aggregation.
About the author
The work was performed at the Institute of Experimental Physics SAS in Kosice, Slovakia, and ISMN-CNR in Bologna, Italy. Dr Zuzana Gazova, Dr Jaroslava Bagelova and PhD student Andrea Bellova are members of the Protein Amyloid Aggregation Group in the Department of Biophysics at IEP SAS. They have experience in the biochemistry that underlies the aggregation process leading to the production of amyloid fibrillar structures and identification of the inhibitors of aggregation. Dr Koneracka, Dr Kopcansky, Dr Tomasovicova and Dr Timko are members of the Department of Magnetism at IEP SAS and deal with magnetic nanoparticles, magnetic fluids and their composites. The team has great experience in the preparation of magnetic monodomain ferri- or ferromagnetic particles as well as bacterial magnetic particles (magnetosomes) produced by mineralization process in magnetotactic bacteria. Dr Fabio Biscarini is head of nanotechnology at the Multifunctional Materials Research Division at ISMN-CNR in Bologna. He is author of more than 140 publications and co-inventor of 16 patents. Dr Eva Bystrenova is a research scientist at ISMN-CNR in Bologna with expertise in nanotechnology (soft lithography, SPM, fluorescence microscopy) for biological applications. Dr Francesco Valle is a researcher at ISMN-CNR in Bologna with expertise in biophysics, protein interactions at surfaces, interfaces and force spectroscopy of proteins.