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O1‐07‐02: Role of the AT8 Alzheimer's disease phosphorylation of tau on mitochondrial transport and inter‐microtubule spacing
Author(s) -
Shahpasand Kourosh,
Hasegawa Masato,
Hisanaga Shinichi
Publication year - 2012
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.2012.05.240
Subject(s) - microtubule , phosphorylation , microbiology and biotechnology , axoplasmic transport , tau protein , hyperphosphorylation , microtubule associated protein , mitochondrion , tauopathy , chemistry , cyclin dependent kinase 5 , biology , neurodegeneration , alzheimer's disease , medicine , protein kinase a , mitogen activated protein kinase kinase , disease
but not GSK3̂I6, reduced BACE1-mediated cleavage of APP and Ab production by decreasing BACE1 gene transcription and expression. The regulation of BACE1 gene expression by GSK3b is dependent on NF̂IB signaling. Specific inhibition of GSK3 signaling markedly reduced Ab deposition and neuritic plaque formation, and rescued memory deficits in the double transgenic AD model mice. Taken together, our data provide evidence for regulation of BACE1 expression and AD pathogenesis by GSK3b and that inhibition of GSK3 signaling can reduce Ab neuropathology and alleviate memory deficits in AD model mice. Conclusions: Our study suggests that interventions that target the b-isoform of GSK3 specifically may be a safe and effective approach for treating AD.