To study the disease, the researchers derived induced pluripotent stem cells (iPS cells) from small samples of skin from patients with Machado-Joseph disease. They then converted the iPS cells into brain stem cells, creating an ever-ready supply of neurons for their investigations. The cause of the disorder is a repeating sequence in the ATXN3 gene, which causes a build-up of the Ataxin protein, damaging neurons in the brain. This genome sequence was present in the patients’ cells and therefore also in the iPS cells.
The engineered nerve cells were stimulated using electrical currents. The researchers were able to determine that the formation of the harmful protein aggregates is directly related with a neuron’s electrical activity. A key role is played by an enzyme called calpain, which is activated by increased calcium levels in the nerve cells when stimulated by the electrical current.
Sources:
http://www.biotechnologie.de/BIO
http://www.dzne.de/
Abstract: Koch, P., Breuer, P., Peitz, M., Jungverdorben, J., Kesavan, J., Poppe, D., Doerr, J., Ladewig, J., Mertens, J., Tüting, T., Hoffmann, P., Klockgether, T., Evert, B. O., Wüllner, U. & Brüstle, O. (2011): Excitation-induced ataxin-3 aggregation in neurons from patients with Machado–Joseph disease. Nature (Vorabveröffentlichung doi:10.1038/nature10671). http://www.nature.com