Researchers have developed synthetic peptides that could target and reduce toxic protein aggregates, which are supposed to cause disease, a new study finds.

The study was published in the Proceedings of the

is a caused by the aggregation of the toxic protein. Neurons in the human brain make a protein called Such proteins on their own, called monomers of amyloid beta, perform important tasks for neurons.

But in the brains of people with disease, monomers abandoned their jobs and get joined together. First, they form oligomers- small clusters of up to a dozen proteins- then longer strands and finally large deposits called plaques.

For years, scientists believed that plaques triggered the cognitive impairments characteristic of But newer research implicated the smaller aggregates of as the toxic elements of this

The research reported that the synthetic peptides- which are designed to fold into a structure known as an sheet- can block amyloid beta aggregation at the early and most toxic stage when oligomers form.

The team showed that the synthetic sheet's blocking activity reduced amyloid beta-triggered toxicity in human neural cells grown in culture, and inhibited amyloid beta oligomers in two laboratory animal models for Alzheimer's.

These findings add evidence to the growing consensus that amyloid beta oligomers- not plaques- are the toxic agents behind

The results also indicated that synthetic sheets could form the basis of therapeutics to clear toxic oligomers in people, according to

"This is about targeting a specific structure of amyloid beta formed by the toxic oligomers. What we have shown here is that we can design and build synthetic alpha sheets with complementary structures to inhibit aggregation and toxicity of amyloid beta while leaving the biologically active monomers intact," said Daggett.

Using both novel and conventional spectroscopic techniques, Daggett's team observed the individual stages of development of amyloid beta clusters, from monomers to six- and 12-protein oligomers all the way up to plaques, in human neural cell lines.

The researchers confirmed that the oligomer stages were most toxic to the neurons, which agrees with clinical reports of amyloid beta plaques in the brains of people who don't have Alzheimer's.

"Amyloid beta definitely plays a lead role in Alzheimer's disease, but while historically attention has been on the plaques, more and more research instead indicates that amyloid beta oligomers are the toxic agents that disrupt neurons," said Daggett.

The synthetic alpha sheet also protected laboratory animals from toxic oligomer damage. In brain tissue samples from mice, the team observed an up to 82 per cent drop in amyloid beta oligomer levels after treatment with a synthetic alpha sheet

Administering a synthetic alpha sheet to living mice triggered a 40 per cent drop in amyloid beta oligomer levels after 24 hours.

In the common laboratory worm Caenorhabditis elegans (C. elegans), another model for Alzheimer's disease, treatment with synthetic alpha sheets delayed the onset of

For the current study, the researchers also created a novel laboratory assay that uses a synthetic alpha sheet to measure levels of amyloid beta oligomers. They believe this assay could form the basis of a clinical test to detect toxic oligomers in people before the onset of Alzheimer's symptoms.

"What we are really after are potential therapeutics against amyloid beta and diagnostic measures to detect toxic oligomers in people. Those are the next steps," said Daggett.

(This story has not been edited by Business Standard staff and is auto-generated from a syndicated feed.)

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