The mechanism of tau toxicity is still unclear. Here we report that recombinant tau oligomers and monomers, intraventricularly injected in mice with a pure human tau background, foster tau pathology through different mechanisms. Oligomeric forms of tau alter the conformation of tau in a paired helical filament-like manner. This effect occurs without tau hyperphosphorylation as well as activation of specific kinases, suggesting that oligomers of tau induce tau assembly through a nucleation effect. Monomers, in turn, induce neurodegeneration through a calpain-mediated tau cleavage that leads to accumulation of a 17 kDa neurotoxic peptide and induction of apoptotic cell death.

Dual Mechanism of toxicity for extracellular injection of Tau oligomers versus monomers in human Tau mice

MANASSERO, GIUSI;GUGLIELMOTTO, Michela;MONTELEONE, DEBORA;VASCIAVEO, VALERIA;TAMAGNO, Elena;
2017

Abstract

The mechanism of tau toxicity is still unclear. Here we report that recombinant tau oligomers and monomers, intraventricularly injected in mice with a pure human tau background, foster tau pathology through different mechanisms. Oligomeric forms of tau alter the conformation of tau in a paired helical filament-like manner. This effect occurs without tau hyperphosphorylation as well as activation of specific kinases, suggesting that oligomers of tau induce tau assembly through a nucleation effect. Monomers, in turn, induce neurodegeneration through a calpain-mediated tau cleavage that leads to accumulation of a 17 kDa neurotoxic peptide and induction of apoptotic cell death.
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www.iospress.nl/journal/journal-of-alzheimers-disease/
Alzheimer's disease; hTau mice; paired helical filaments; tau protein;
Manassero, G; Guglielmotto, M; Monteleone, D; Vasciaveo, V; Butenko, O; Tamagno, E; Arancio, O; Tabaton, M
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/1656122
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