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P3‐056: OVEREXPRESSION OF HUMAN TAU40 DISRUPTS MITOCHONDRIAL DYNAMIC AND THE FUNCTIONS WITH A SUBSEQUENT NEURODEGENERATION
Author(s) -
Wang JianZhi,
Li XiaChun
Publication year - 2014
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.2014.05.1144
Subject(s) - microbiology and biotechnology , mitochondrial fusion , pink1 , mfn2 , mitochondrion , mfn1 , biology , neurodegeneration , parkin , mitophagy , biochemistry , autophagy , mitochondrial dna , apoptosis , medicine , disease , gene , pathology , parkinson's disease
constructed the plasmids of Bip and Sil1 and transfected them into HEK293/ tau or N2a cells. Tau hyperphosphorylation and glycogen synthase kinase3b (GSK-3b) activation were detected by by Western blotting. The association with tau, Bip and GSK-3b was analysised by immunoprecipitation. Results: Bip was found increased while Sil1 was reduced in the brains of Tg2576 mice compared to the age-matched control mice. We constructed Bip-EGFP plasmid and transfected it into HEK293/tau or N2a cells and found that overexpression of Bip induced tau hyperphosphorylation via activating GSK-3b, and increased association with tau and GSK-3b. Transfection of Sil1 plasmid could inverse the above. Conclusions: Increasing of Bip in AD brain and ER stress may be an important upstream factor of tau hyperphosphorylation.