Michel Goedert FRS, FMedSci

Michel Goedert is Staff Scientist & Joint Head of the Neurobiology Division, MRC Laboratory of Molecular Biology. He is distinguished for elucidating the central role played by microtubule-associated protein tau and the protein synuclein in the pathogenesis of a large number of neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. He demonstrated that tau is an integral component of the paired helical filament, the major fibrous component of the intraneuronal lesions found in the brains of Alzheimer’s disease patients. He defined tau at a molecular level by showing that the brain contains six isoforms generated from a single gene through alternative mRNA splicing. He found that all tau isoforms are incorporated into paired helical filaments and that they are in an abnormally phosphorylated state, resulting in a reduced ability to bind to microtubules. He subsequently discovered that sulphated glycosaminoglycans induce bulk assembly of tau into Alzheimer-like filaments, and provided evidence that such an interaction may be a critical pathological event in the formation of Alzheimer lesions. He and his colleagues were amongst the first to report a mutation in the tau gene in inherited dementia, which firmly establishes that tau pathology is central to the neurodegenerative process. More recently, Goedert and colleagues discovered that alpha-synuclein, a protein that is mutated in some inherited cases of Parkinson’s disease, is the major component of Lewy bodies and Lewy neurites, the intraneuronal filamentous lesions found in the brains of people with Parkinson’s disease and dementia with Lewy bodies. They subsequently identified multiple system atrophy as an a-synucleinopathy.