Understanding Neurodegenerative Diseases

Understanding Neurodegenerative Diseases By Michel Goedert LMB Seminar for non-scientists Alzheimer’s and Parkinson’s, which affect more than 50 million people worldwide, are the most common neurodegenerative diseases. Patients with Alzheimer’s disease suffer from a profound loss of memory and other cognitive functions, whereas patients with Parkinson’s disease have a severe movement disorder. In their brains, one finds abundant filamentous inclusions. Work on these inclusions began at LMB in 1983. In Alzheimer’s disease, they are plaques and tangles that are made of the proteins beta-amyloid and tau, respectively; in Parkinson’s disease, they are Lewy bodies and neurites made of alpha-synuclein. These proteins normally exist in a soluble form and it is their assembly into filaments and the ensuing neurodegeneration that account for Alzheimer’s and Parkinson’s diseases. Filamentous tau or alpha-synuclein inclusions also define other neurodegenerative diseases, including progressive supranuclear palsy, Pick’s disease and multiple system atrophy. This raises the question if structurally distinct filaments are characteristic of different diseases. Since 2017, in collaboration with Sjors Scheres, we have been using electron cryo-microscopy to determine the structures of tau and alpha-synuclein filaments from brain. So far, we have shown that each neurodegenerative disease is characterised by its own filament fold and that some diseases share the same fold. Differences in folds are between some diseases, not between individuals with a given disease. Knowledge of the structures of disease filaments will probably lead to the development of better experimental models, safe and potent inhibitors of assembly and imaging agents with increased specificity and sensitivity. -- About the MRC Laboratory of Molecular Biology (LMB): The LMB is one of the world's leading research institutes. Discoveries and inventions developed at the LMB, for example DNA sequencing and methods to determine the structure of proteins, have revolutionised all areas of biology. Its scientists work to advance understanding of biological processes at the molecular level. This information will help us to understand the workings of complex systems, such as the immune system and the brain, and solve key problems in human health. More links: Official Site: https://www2.mrc-lmb.cam.ac.uk/ Facebook: https://www.facebook.com/MRC.LMB Twitter: https://twitter.com/MRC_LMB Instagram: https://www.instagram.com/mrc_lmb/ LinkedIn: https://www.linkedin.com/company/mrc-laboratory-of-molecular-biology Click here to subscribe to MRC Laboratory of Molecular Biology on YouTube: