Brichos protein may prevent brain damage in Alzheimer’s
Researchers at Karolinska Institutet and the universities in Lund and Cambridge have found that fragments from the human Brichos protein have 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.
Studies on brain tissue from mice show that the Alzheimer’s disease-peptide amyloid-beta (A-beta) degrades oscillations of the neuronal network in the gamma-frequency band (30-80 Hz), which are important for memory and learning. However, in the current study 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.
The contributing scientists from Karolinska Institutet were Jenny Presto, Firoz Roshan Kurudenkandy, Henrik Biverstål, Lisa Dolfe, Janne Johansson, and André Fisahn. The study was funded by, amongst other organizations, the chiff Foundation, the Swedish Research Council, the Crafoord Foundation, the Swedish Alzheimer Foundation, the Frances and Augustus Newman Foundation the European Research Council, the Strategic Program in Neurosciences at the Karolinska Institute, the Swiss National Science Foundation, and the Wellcome Trust.
The molecular chaperone Brichos breaks the catalytic cycle that generates toxic Aβ oligomers
Samuel I. A. Cohen, Paolo Arosio, Jenny Presto, Firoz Roshan Kurudenkandy, Henrik Biverstål, 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