The significance of tau and alpha-synuclein inclusions in neurodegenerative diseases.
Intracellular filamentous inclusions made of either the microtubule-associated protein tau or the protein alpha-synuclein define the majority of cases of neurodegenerative disease. Mutations in the tau gene in familial forms of frontotemporal dementia and in the alpha-synuclein gene in familial cases of Parkinson's disease have provided causal links between the dysfunction of these proteins and neurodegeneration. Over the past year, several novel tau gene mutations have been identified and more has been learned about possible mechanisms by which tau gene mutations lead to frontotemporal dementia. Experimental animal models have provided a link between tau filament formation and nerve cell degeneration. Along similar lines, animal models have been produced that result in the formation of alpha-synuclein filaments and the degeneration of dopaminergic nerve cells. Building on previous work, synthetic alpha-synuclein filaments have been shown to exhibit the characteristics of amyloid.
Goedert
M
M
MRC Laboratory of Molecular Biology, Hills Road, CB2 2QH, Cambridge, UK. mg@mrc-lmb.cam.ac.uk
D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D002479:Inclusion Bodies / Q000235:genetics / Q000473:pathology*; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000502:physiology; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000473:pathology*; D051843:Synucleins; D051844:alpha-Synuclein; D016875:tau Proteins / Q000235:genetics* / Q000502:physiology
D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein; D016875:tau Proteins