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P3‐123: Which attributes of tau mediate toxicity: Phosphorylation or aggregation?
Author(s) -
Cowan Catherine,
Sealey Megan,
Allan Douglas,
Mudher Amritpal
Publication year - 2011
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2011.05.1564
Subject(s) - microtubule , axoplasmic transport , microbiology and biotechnology , phosphorylation , cytoplasm , tau protein , synapse , biology , tauopathy , microtubule associated protein , chemistry , neuron , neuroscience , neurodegeneration , biophysics , alzheimer's disease , medicine , disease
For the Jcasp model, SET expression was performed by real time PCR. Results:When the Jcasp peptide was internalized, SET moved to the cytoplasm, but no over expression of the protein preceded the delocalization. The delocalized SET was mainly entire and few fragments of small sizes were observed. When the whole SET protein was internalized it localized in the cytoplasm and moved to the nucleus after 3h. In that case, the protein was mainly entire in the nucleus after 5h. In each model, when the protein was in the cytoplasm it induced an increase of Tau phosphorylation at epitopes Ser 202, Thr 205, Ser422. Conclusions: The delocalization of SET from the nucleus to the cytoplasm does not require its over expression and/or a previous cleavage of the protein in the nucleus. No additional cleavage of SET is detected when SET is directly internalized in the cytoplasm. The presence of the protein in the cytoplasm is associated to an increase of Tau phosphorylation at sites detected in Alzheimer patient brains, suggesting that the delocalization of SETaccelerates the development of the pathology through Tau hyperphosphorylation.