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P1‐369: Overexpression of puromycin sensitive aminopeptidase (PSA/NPEPPS) reduces soluble tau and delays development of neuropathology in PSA/TAU‐P301L double transgenic mice
Author(s) -
Karsten Stanislav L.,
Parfenova Liubov,
Lau Kimbley,
Vi Nancy,
Hui Maria,
Gray Michelle,
Yang X. William,
Hui Koon-Sea,
Kudo Lili C.
Publication year - 2010
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.2010.05.923
Subject(s) - neuroprotection , neurodegeneration , genetically modified mouse , biology , transgene , in vivo , endocrinology , medicine , microbiology and biotechnology , neuroscience , biochemistry , disease , gene
Results: We found that pseudophosphorylated tau aggregates in cells when Thr 212 is mutated to Glu (Ps-tau), suggesting that phosphorylation at this site facilitates tau self-assembly. The expression of tau pseudophosphorylated at Thr212, Thr231, and Ser262 disrupts the microtubules when co-transfected with fluorescent tubulin. EB-1 is a protein that binds to the growing end of the microtubules. Cells stably transfected with fluorescent EB-1 are used to visualize the dynamics of these filaments in the live cells. These cells were transfected with an inducible system to express tau upon withdraw of doxycycline (TET-off). The effect of Ps-tau on these cells was also studied. Conclusions: These findings suggest that tau phosphorylation at Thr 212 facilitates tau self-aggregation, and that the combination of phosphorylation at Thr212, 231 and Ser262 in the same tau molecule can trigger toxic reaction.