Dual Mechanism of Toxicity for Extracellular Injection of Tau Oligomers versus Monomers in Human Tau Mice

作者:Manassero Giusi; Guglielmotto Michela; Monteleone Debora; Vasciaveo Valeria; Butenko Olena; Tamagno Elena; Arancio Ottavio; Tabaton Massimo*
来源:Journal of Alzheimer's Disease, 2017, 59(2): 743-751.
DOI:10.3233/JAD-170298

摘要

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.

  • 出版日期2017