Designer Protein Offers New Hope For Alzheimer’s Studies

Summary: Researchers have designed a new protein to better understand why nerve cells die in people with Alzheimer’s disease.

Source: University of Sussex.

A new protein which will help scientists to understand why nerve cells die in people with Alzheimer’s disease has been designed in a University of Sussex laboratory.

In people with Alzheimer’s, Amyloid-beta (Abeta) proteins stick together to make amyloid fibrils which form clumps between neurons in the brain. It’s believed the build-up of these clumps causes brain cells to die, leading to the cognitive decline in patients suffering from the disease.

It is not known why this particular protein’s “stickiness” causes cells to die and scientists have been unable to properly test whether the sticky clumps of Abeta proteins have different effects, compared with individual proteins that are not stuck together.

Now University of Sussex scientists have created a new protein which closely resembles the Abeta protein in size and shape, but contains two different amino acids (the building blocks that proteins are made up of). These changes mean that the new protein does not form amyloid fibres or sticky clumps, and, unlike Abeta, is not toxic to nerve cells, according to a study in the open access Nature Publishing Group journal Scientific Reports.

The new protein will be an essential laboratory tool for researchers working to understand the causes and role Abeta plays in Alzheimer’s disease. The scientists who designed it are now working closely with the Sussex Innovation Centre, the University’s business-incubation hub, to research commercial opportunities for the protein.

Dr Karen Marshall, who led on the study, said: “Understanding how the brain protein Abeta causes nerve cell death in Alzheimer’s patients is key if we are to find a cure for this disease.

“Our study clearly shows that the aggregation of Abeta into bigger species is critical in its ability to kill cells. Stopping the protein aggregating in people with Alzheimer’s could slow down the progression symptoms of the disease. We hope to work towards finding a strategy to do this in the lab and reverse the damaging effects of toxic Abeta.”

Image shows a brain scan.
The new protein will be an essential laboratory tool for researchers working to understand the causes and role Abeta plays in Alzheimer’s disease. NeuroscienceNews.com image is adapted from the University of Sussex press release.

Professor Louise Serpell, a senior author on the study and co-director of the University of Sussex’s Dementia Research Group, said: “This is a really exciting new tool that will contribute to research to uncover the causes for Alzheimer’s disease and enable tangible progress to be made towards finding targets for therapy.”

Peter Lane, Innovation Support Manager at the Sussex Innovation Centre, said: “This is a really exciting development. The Centre is thrilled to be working alongside Professor Serpell to make sure the benefits offered by this new laboratory tool are made widely available to the Alzheimer’s research community in the very near future.”

About this Alzheimer’s disease research article

Source: Lynsey Ford – University of Sussex
Image Source: This NeuroscienceNews.com image is adapted from the University of Sussex press release.
Original Research: Full open access research for “A critical role for the self-assembly of Amyloid-β1-42 in neurodegeneration” by Karen E. Marshall, Devkee M. Vadukul, Liza Dahal, Alina Theisen, Milena W. Fowler, Youssra Al-Hilaly, Lenzie Ford, György Kemenes, Iain J. Day, Kevin Staras and Louise C. Serpell in Scientific Reports. Published online July 22 2016 doi:10.1038/srep30182

Cite This NeuroscienceNews.com Article

[cbtabs][cbtab title=”MLA”]University of Sussex. “Designer Protein Offers New Hope For Alzheimer’s Studies.” NeuroscienceNews. NeuroscienceNews, 22 July 2016.
<https://neurosciencenews.com/alzheimers-designer-protein-4727/>.[/cbtab][cbtab title=”APA”]University of Sussex. (2016, July 22). Designer Protein Offers New Hope For Alzheimer’s Studies. NeuroscienceNew. Retrieved July 22, 2016 from https://neurosciencenews.com/alzheimers-designer-protein-4727/[/cbtab][cbtab title=”Chicago”]University of Sussex. “Designer Protein Offers New Hope For Alzheimer’s Studies.” https://neurosciencenews.com/alzheimers-designer-protein-4727/ (accessed July 22, 2016).[/cbtab][/cbtabs]


Abstract

A critical role for the self-assembly of Amyloid-β1-42 in neurodegeneration

Amyloid β1-42 (Aβ1-42) plays a central role in Alzheimer’s disease. The link between structure, assembly and neuronal toxicity of this peptide is of major current interest but still poorly defined. Here, we explored this relationship by rationally designing a variant form of Aβ1-42 (vAβ1-42) differing in only two amino acids. Unlike Aβ1-42, we found that the variant does not self-assemble, nor is it toxic to neuronal cells. Moreover, while Aβ1-42 oligomers impact on synaptic function, vAβ1-42 does not. In a living animal model system we demonstrate that only Aβ1-42 leads to memory deficits. Our findings underline a key role for peptide sequence in the ability to assemble and form toxic structures. Furthermore, our non-toxic variant satisfies an unmet demand for a closely related control peptide for Aβ1-42 cellular studies of disease pathology, offering a new opportunity to decipher the mechanisms that accompany Aβ1-42-induced toxicity leading to neurodegeneration.

“A critical role for the self-assembly of Amyloid-β1-42 in neurodegeneration” by Karen E. Marshall, Devkee M. Vadukul, Liza Dahal, Alina Theisen, Milena W. Fowler, Youssra Al-Hilaly, Lenzie Ford, György Kemenes, Iain J. Day, Kevin Staras and Louise C. Serpell in Scientific Reports. Published online July 22 2016 doi:10.1038/srep30182

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