title: Pathogenesis of the tauopathies.
abstract: Microtubule-associated protein tau is the most commonly misfolded protein in human neurodegenerative diseases, where it becomes hyperphosphorylated and filamentous. Mutations in MAPT, the tau gene, cause approximately 5% of cases of frontotemporal dementia. They are frequently accompanied by parkinsonism. The existence of MAPT mutations has established that dysfunction of tau protein is sufficient to cause neurodegeneration and dementia. However, most tauopathies are not inherited in a dominant manner. The hyperphosphorylated sites are similar between diseases, but filament morphologies and tau isoform compositions vary. This is consistent with the existence of multiple tau conformers and recent findings have provided experimental support for this concept.
authors.affiliation: MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 0QH, UK. mg@mrc-lmb.cam.ac.uk
authors.forename: Michel
authors.initials: M
authors.lastname: Goedert
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Spillantini
mesh_terms: D006801:Humans; D002479:Inclusion Bodies / Q000473:pathology; D007382:Intermediate Filaments / Q000473:pathology; D009154:Mutation; D020734:Parkinsonian Disorders / Q000235:genetics / Q000473:pathology; D010766:Phosphorylation; D017510:Protein Folding; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D024801:Tauopathies / Q000209:etiology* / Q000235:genetics* / Q000473:pathology*; D016875:tau Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
chemical_list: D020033:Protein Isoforms; D016875:tau Proteins