Researchers working at Karolinska Institutet and the universities in Lund, Cambridge and Tallinn have found that a human Brichos protein has the ability to prevent neuronal and brain damage caused by amyloid-beta in Alzheimer’s disease. The findings are being published in the journal Nature Structural and Molecular Biology.
Professor Jan Johansson and Dr Jenny Presto are running a fruitful collaboration between Tallinn University and Karolinska Institutet, Sweden, leading research groups at both universities. Their research group has since 2006 been studying proteins containing a so called Brichos domain, and they have found that Brichos is able to prevent other proteins from sticking together and form toxic clumps – so called plaques, for example found in the brain of Alzheimer disease patients.
Now the Karolinska/Tallinn group has made a research breakthrough, in collaboration with scientists from the universities in Lund and Cambridge. Studies on brain tissue from mice show that the Alzheimer’s disease-peptide amyloid-beta (A-beta) degrades oscillations in the brain, which are important for memory and learning. However, in the current study the researchers show that in the presence of Brichos this degradation was completely prevented. The team also studied A-beta in test tubes with and without Brichos, and found that the preventive effects are associated with a highly specific function of this protein. Brichos was found to bind to aggregated forms of A-beta, thereby blocking the surfaces that would otherwise be responsible for generation of neurotoxic activity and cell death.
Alzheimer’s disease is a progressive brain disorder and is the most common form of dementia. Unfortunately there are today no available disease-modifying therapies against Alzheimer, only symptomatic therapies are being used.
“We believe that we have found a method to block the progress of Alzheimer’s at a crucial stage in its development, which now has to be further investigated and evaluated as a potential new treatment strategy for Alzheimers disease.”, the researchers speculate.
Publication: “A molecular chaperone breaks the catalytic cycle that generates toxic Aβ oligomers”, Samuel I. A. Cohen, Paolo Arosio, Jenny Presto, Firoz Roshan Kurudenkandy, Henrik Biverstal, Lisa Dolfe, Christopher Dunning, Xiaoting Yang, Birgitta Frohm, Michele Vendruscolo, Jan Johansson, Christopher M. Dobson, André Fisahn, Tuomas P. J. Knowles, and Sara Linse, Nature Structural & Molecular Biology, advance online publication 16 February 2015, doi: 10.1038/nsmb.2971