May 202011

Researchers say that sharp-edged nanoparticles can block neurodegenerative proteins that impede cognitive function.

The next challenge is making nanoparticles in this shape out of nontoxic materials.

Nanoparticles have been investigated in recent years as tools for defending the brain against neurotoxic proteins that may contribute to the onset of several different neurodegenerative disorders including Alzheimer’s disease. Such proteins, in particular amyloid-beta peptides, are thought to play a role depositing fibrous plaques on the brain that damage synapses(the contact points between neurons) and lead to a decline in cognitive capabilities.

During the onset of Alzheimer’s, amyloid beta collects in the brain centers that form new memories. As the disease progresses, these toxic protein fragments block neurotransmitters from reaching receptors on neurons. The promise of nanoparticles is that their capacity to mimic some biological functions as well as penetrate the blood–brain barrier will enable them to stop the growth of neuron-blocking fibrils better than drug compounds that might contain some variation of short peptides, antibodies or proteins—such as human serum albumin  (HSA) protein. (There currently are no anti-Alzheimer’s drugs on the market.) Whereas such compounds have been shown to interfere with fibril formation, researchers are hoping that inorganic nanoparticles can do so more effectively.

Although the nanotech approach has great potential, the challenges are many, including finding a nanoparticle material that is effective yet also biocompatible and nontoxic. Another source of controversy: some nanoparticles that have been studied, including quantum dots and carbon nanotubes, seem to actually promote or accelerate fibrillation rather than prevent it.

A multidisciplinary team of researchers from the University of Michigan at Ann Arbor(U.M.) and South Korea’s Kyungpook National University claim to have resolved at least some of nanotech’s shortcomings in tackling amyloid-beta peptides. In a study published online last month in Angewandte Chemie International Edition the researchers describe inhibiting amyloid-beta fibrillation using cadmium telluride (CdTe) nanoparticles with a  tetrahedral shape and negative charge.

“We decided to look at how inorganic materials can affect fibrillation of amyloid peptides, which are small proteinlike structures that form extended assemblies that look like nanofibers,” says Nicholas Kotov, a U.M. chemical engineering professor who led the study.

Whereas as these CdTe nanoparticles are not biocompatible and would be toxic in the body, the researchers chose them because they resemble in size, charge and behavior some of the proteins that have proved effective in blocking fibrillation.

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