title: Deferoxamine inhibits iron induced hippocampal tau phosphorylation in the Alzheimer transgenic mouse brain.
abstract: Prior work has shown that iron interacts with hyperphosphorylated tau, which contributes to the formation of neurofibrillary tangles (NFTs) in Alzheimer's disease (AD), whereas iron chelator desferrioxamine (DFO) slows down the clinical progression of the cognitive decline associated with this disease. However, the effects of DFO on tau phosphorylation in the presence or absence of iron have yet to be determined. Using amyloid precursor protein (APP) and presenilin 1 (PS1) double transgenic mouse brain as a model system, we investigated the effects and potential mechanisms of intranasal administration of DFO on iron induced abnormal tau phosphorylation. High-dose iron treatment markedly increased the levels of tau phosphorylation at the sites of Thr205, Thr231 and Ser396, whereas highly induced tau phosphorylation was abolished by intranasal administration of DFO in APP/PS1 transgenic mice. Moreover, DFO intranasal administration also decreases Fe-induced the activities of cyclin-dependent kinase 5 (CDK5) and glycogen synthase kinase 3β (GSK3β), which in turn suppressing tau phosphorylation. Cumulatively, our data show that intranasal DFO treatment exerts its suppressive effects on iron induced tau phosphorylation via CDK5 and GSK3β pathways. More importantly, elucidation of DFO mechanism in suppressing tau phosphorylation may provide insights for developing therapeutic strategies to combat AD.
authors.affiliation: College of Life and Health Sciences, Northeastern University, Shenyang 110004, PR China.
authors.forename: Chuang
authors.initials: C
authors.lastname: Guo
authors.forename: Pu
authors.initials: P
authors.lastname: Wang
authors.forename: Man-Li
authors.initials: ML
authors.lastname: Zhong
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Xue-Shi
authors.initials: XS
authors.lastname: Huang
authors.forename: Jia-Yi
authors.initials: JY
authors.lastname: Li
authors.forename: Zhan-You
authors.initials: ZY
authors.lastname: Wang
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D015153:Blotting, Western; D003676:Deferoxamine / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007150:Immunohistochemistry; D007501:Iron / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010766:Phosphorylation; D053764:Presenilin-1 / Q000235:genetics; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1; C580804:presenilin 1, mouse; D016875:tau Proteins; D007501:Iron; D003676:Deferoxamine