Neurodegenerative precursor structure revealed
10 Jul 2017 by Evoluted New Media
Scientists have uncovered the atomic structure of a protein strongly associated with Alzheimer’s disease, using cryo-electron microscopy.
Scientists have uncovered the atomic structure of a protein strongly associated with Alzheimer’s disease, using cryo-electron microscopy.
Almost three decades ago, scientists identified the tau protein was involved in Alzheimer’s and other neurodegenerative diseases, but until now, its atomic structure was never understood. The breakthrough came after researchers developed new software to calculate the protein’s atomic arrangement.
Dr Sjors Scheres, from the Medical Research Council (MRC) Laboratory of Molecular Biology and senior author of the study, said: “It’s very exciting that we were able to use this new technique to visualise filaments from a diseased brain as previous work depended on artificial samples assembled in the laboratory.”
Tau proteins form filaments inside nerve cells in the brain, whereas amyloid beta proteins forms filaments outside of cells. The scientists extracted tau filaments from a patient who had died with Alzheimer’s disease, before analysis with cryo-electron microscopy. This technique, which over the last couple of years has risen in popularity, captures highly-detailed atomic resolution images of proteins.
Pharmaceutical advantages
Dr Scheres added: “Knowing which parts of tau are important for filament formation is relevant for the development of drugs. For example, many pharmaceutical companies are currently using different parts of tau in tests to measure the effect of different drugs on filament formation; this new knowledge should significantly increase the accuracy of such tests."Dr Michel Goedert, one of the scientists involved in first identifying tau proteins and senior author, said: “Until now the high-resolution structures of tau or any other disease-causing filaments from human brain tissue have remained unknown. This new work will help to develop better compounds for diagnosing and treating Alzheimer's and other diseases which involve defective tau.”
The researchers were funded by the MRC, the EU and various US institutions with the study published in Nature.
