Towards an Amyloid-β Sequestering Nanoparticle to Block Protein Aggregation
Researchers here report on development of a nanoparticle that sweeps up the amyloid-β associated with Alzheimer's disease, preventing it from forming aggregates. When stuck to the nanoparticle, amyloid-β will not generate the harmful biochemistry that arises as a consequence of the formation of aggregated protein structures. This is an interesting approach to reducing levels of amyloid-β, albeit at a very early stage in development. As always, one must note that there is considerable debate over whether amyloid-β clearance is either the right approach to Alzheimer's disease, or sufficient in and of itself to prevent pathology. Amyloid-β aggregation is clearly harmful, the evidence is plentiful on that front, but it is possible that its presence is a side-effect of a more dominant disease mechanism, such as, for example, chronic inflammation derived from persistent infection.
People who are affected by Alzheimer's disease have a specific type of plaque, made of self-assembled molecules called β-amyloid (Aβ) peptides, that build up in the brain over time. Researchers have developed an approach to prevent plaque formation by engineering a nano-sized device that captures the dangerous peptides before they can self-assemble. The researchers covered the surface of the new nanodevice with fragments of an antibody that recognizes and binds to the Aβ peptides. The surface of the nanodevice is spherical and porous, and its craters maximize the available surface area for the antibodies to cover. More surface area means more capacity for capturing the sticky peptides.
A full antibody molecule can be up to a few dozen nanometers long, which is big in the realm of nanotechnology. However, only a fraction of this antibody is involved in attracting the peptides. To maximize the effectiveness and capacity of the nanodevices, researchers produced tiny fragments of the antibodies to decorate the nanodevice's surface. The scientists constructed the base of the porous, spherical nanodevices out of silica, a material that has long been used in biomedical applications due to its flexibility in synthesis and its nontoxicity in the body. Coated with the antibody fragments, the nanodevices capture and trap the Aβ peptides with high selectivity and strength.
The scientists tested the effectiveness of the devices by comparing how the peptides behaved in the absence and presence of the nanodevices. These studies supported the case that the nanodevices sequester the peptides from the pathway to aggregation by more than 90 percent compared to the control silica particles without the antibody fragments. However, the devices still needed to demonstrate their effectiveness and safety within cells and brains.
Link: https://www.anl.gov/article/nanodevices-for-the-brain-could-thwart-formation-of-alzheimers-plaques