Protein amyloid fibrillation in Parkinson's disease simulated at a nanoscale
Coagulating of proteins in cerebral cells, as is being observed in Parkinson's disease, can be simulated very well in a laboratory. It appears that fibrils formed by proteins that occur in sound cerebral cells, look differently from fibrils shaped by mutant proteins: the deviating protein fibrils are only met with some families that have a hereditary form of Parkinson's disease. Researchers Martijn van Raaij, Ine Segers-Nolten and Vinod Subramaniam of the Biophysical Engineering group at the University of Twente, demonstrate this distinction in their issue in this week's Biophysical Journal. Similar fibrils of other proteins are playing a role in other neurodegenerative illnesses such as Altzheimer's disease and Creutzfeldt-Jacob disease. The research is being funded by FOM Foundation.
Nearly two hundred years after the first publication by the British physician after whom the disease is named, it is still not yet known what causes Parkinson's disease. In addition to clinical research with patients and taking place all over the world, the processes that play a role in this disease are also being investigated at a cellular and molecular level. It is firmly established that coagulation in case of proteins in cerebral cells does occur. Martijn van Raaij has been examining this process by using an Atomic Force Microscope (AMF): a microscope that explores a surface with a needle and that portrays single protein fibrils. The protein -synuclein forms long fibrils during coagulating. This amyloid fibrillation is of importance in search for the causes of Parkinson's disease and some other neurodegenerative diseases. Van Raaij's results also point out in that direction: he has mapped morphological differences between protein fibrils that can be found in just anybody's cerebral cells and fibrils of the mutant protein that is being found in a hereditary form of Parkinson's disease. These differences in shape arise, for instance, in the fibrils' diameter and the distance between the heights that the needle of the microscope meets on the fibrils (see figure).
The article is entitled: 'Quantitative Morphological Analysis Reveals Ultrastructural Diversity of Amyloid Fibrils from α -Synuclein Mutants', Biophysical Journal 91, 2006, and can be downloaded via http://www.biophysj.org/cgi/content/abstract/91/11/L96. The authors are : Martijn E. van Raaij, Ine M.J. Segers-Nolten and Vinod Subramaniam.
For more information, please contact Vinod Subramaniam.