Neutron scattering research at the Department of Energy’s Oak Ridge National Laboratory has revealed clear structural differences in the normal and pathological forms of a protein involved in Huntington’s disease. Huntington’s disease, an incurable neurodegenerative disorder, starts as a genetic mutation that leads to an overabundance of “huntingtin” protein fragments, which form clumps in the brain. Valerie Berthelier of the University of Tennessee Graduate School of Medicine, who co-led the study published in Biophysical Journal with ORNL’s Chris Stanley, said the goal was to establish a baseline understanding of huntingtin’s structure in order to eventually determine the true structural basis of Huntington’s disease. The study’s results showed key differences in the ways mutant and normal huntingtin proteins take shape. The disease protein, for instance, initially forms aggregates of one to two peptides, whereas the normal version makes bigger aggregates, gathering seven or eight peptides together. These data on the very early stages of protein aggregate formation support a growing focus of the research in the amyloid field. Amyloid disorders, such as Parkinson’s, Alzheimer’s and Huntington’s, all involve protein aggregation phenomena leading to a disease.
Perevozchikova, Tatiana et al. “Investigating the Structural Impact of the Glutamine Repeat in Huntingtin Assembly,” Biophysical Journal. 107:2 (2014): 411 – 421. http://www.cell.com/biophysj/abstract/S0006-3495(14)00602-X