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 17kDa neurotoxic peptide and induction of apoptotic cell death.
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Titolo: | Dual Mechanism of Toxicity for Extracellular Injection of Tau Oligomers versus Monomers in Human Tau Mice |
Autori: | |
Data di pubblicazione: | 2017 |
Rivista: | |
Handle: | http://hdl.handle.net/11567/893910 |
Appare nelle tipologie: | 01.01 - Articolo su rivista |