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Category: New published by Shameen Published on: April 21, 2019, 11:14 pm EST Update: April 21, 2019, 11:14 pm EST
Washington: Researchers have developed synthetic peptides that could target and reduce clusters of toxic proteins, supposed to cause Alzheimer's disease, reveals a new study.
The study was published in the Proceedings of the National Academy of Sciences.
Alzheimer's disease is a disease caused by the aggregation of the toxic protein. Neurons in the human brain produce a protein called beta-amyloid. Such proteins, called beta-amyloid monomers, fulfill important tasks for neurons.
But in the brains of people with Alzheimer's disease, amyloid beta-monomers have dropped out of work and united. First, they form oligomers, small clusters of a dozen proteins, then longer strands and finally large deposits called plates.
For years, scientists have thought that plaques cause the cognitive impairments characteristic of Alzheimer's disease. But new research has implicated the smaller aggregates of beta-amyloid as the toxic elements of this disease.
Research has shown that synthetic peptides, designed to fold into a structure called the alpha leaf, can block beta aggregation of amyloid at the early and most toxic stage of oligomer formation.
The team showed that synthetic alpha leaf blocking activity reduced the beta amyloid-induced toxicity in cultured human neural cells and inhibited amyloid beta-oligomers in two animal laboratory models for the disease. Alzheimer.
These findings add evidence to the growing consensus that amyloid beta-oligomers, not plaques, are the toxic agents behind Alzheimer's disease.
The results also indicated that synthetic alpha sheets could form the basis of the therapy for removing toxic oligomers in humans, according to the corresponding author, Valerie Daggett.
"It's about targeting a specific structure of beta-amyloid formed by toxic oligomers. What we have shown here is that we can design and construct synthetic alpha sheets with complementary structures to inhibit the aggregation and toxicity of beta-amyloid while leaving intact the biologically active monomers, "said Daggett .
Daggett's team used conventional and conventional spectroscopic techniques to observe the different stages of development of beta-amyloid clusters, from monomers to six- and twelve-protein oligomers to plaques, in human neural cell lines.
The researchers confirmed that the oligomer stages were the most toxic for neurons, consistent with the clinical reports of beta amyloid plaques in the brains of people without Alzheimer's.
"Beta amyloid definitely plays a major role in Alzheimer's disease, but if attention has always been focused on plaques, more and more research indicates that amyloid beta-oligomers are toxic agents. that disrupt neurons, "said Daggett.
The synthetic alpha sheet also protected laboratory animals from damage by toxic oligomers. In mouse brain tissue samples, the team observed a fall in amyloid beta-oligomer levels of up to 82% after treatment with a synthetic alpha-peptide.
The administration of a synthetic alpha leaf to live mice caused a 40% fall in amyloid beta-oligomeric levels after 24 hours.
In the common laboratory worm Caenorhabditis elegans (C. elegans), another model of Alzheimer's disease, a synthetic alpha leaf treatment delayed the onset of beta-amyloid-induced paralysis.
For the present study, the researchers also created a new laboratory test using a synthetic alpha sheet to measure levels of amyloid beta-oligomers. They believe that this badysis could form the basis of a clinical test to detect toxic oligomers in humans before the onset of Alzheimer's symptoms.
"What we are really looking for are potential treatments for beta amyloid and diagnostic measures to detect toxic oligomers in humans. These are the next steps, "said Daggett.
Source: ANI
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