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Dual Mechanism of Toxicity for Extracellular Injection of Tau Oligomers versus Monomers in Human Tau Mice
- Source :
- J Alzheimers Dis
- Publication Year :
- 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.
- Subjects :
- 0301 basic medicine
Peptide
law.invention
Mice
0302 clinical medicine
law
Phosphorylation
bcl-2-Associated X Protein
chemistry.chemical_classification
biology
Chemistry
Kinase
Calpain
General Neuroscience
Neurodegeneration
General Medicine
Alzheimer's disease
Recombinant Proteins
Clinical Psychology
Biochemistry
hTau mice
paired helical filaments
tau protein
Geriatrics and Gerontology
Psychiatry and Mental Health
Proto-Oncogene Proteins c-bcl-2
Toxicity
Recombinant DNA
Neurotoxicity Syndromes
Signal Transduction
Tau protein
Green Fluorescent Proteins
Mice, Transgenic
tau Proteins
Cleavage (embryo)
Article
03 medical and health sciences
mental disorders
medicine
Extracellular
Animals
Humans
Injections, Intraventricular
Extracellular Fluid
medicine.disease
Disease Models, Animal
030104 developmental biology
biology.protein
Biophysics
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 18758908
- Volume :
- 59
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Journal of Alzheimer's disease : JAD
- Accession number :
- edsair.doi.dedup.....9fc586f1fbda8b316c1a99a315fbf338