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Iron Induced Hippocampal Tau Phosphorylation
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ironjustice
Feb 6, 2013, 9:00:18 PM2/6/13
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Deferoxamine inhibits iron induced hippocampal tau phosphorylation in
the Alzheimer transgenic mouse brain
Neurochemistry International
Volume 62, Issue 2, January 2013, Pages 165–172
Chuang Guoa, b, 1, Pu Wanga, 1, Man-Li Zhongc, Tao Wanga, Xue-Shi
Huanga, Jia-Yi Lia, Zhan-You Wanga, ,
a College of Life and Health Sciences, Northeastern University,
Shenyang 110004, PR China
b Department of Anatomy, Hebei United University at Qinhuangdao,
Qinhuangdao 066001, PR China
c Department of Pathophysiology, China Medical University, Shenyang
110001, PR China
Corresponding author. Tel./fax: +86 24 22529997.
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.
http://dx.doi.org/10.1016/j.neuint.2012.12.005
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the Alzheimer transgenic mouse brain
Neurochemistry International
Volume 62, Issue 2, January 2013, Pages 165–172
Chuang Guoa, b, 1, Pu Wanga, 1, Man-Li Zhongc, Tao Wanga, Xue-Shi
Huanga, Jia-Yi Lia, Zhan-You Wanga, ,
a College of Life and Health Sciences, Northeastern University,
Shenyang 110004, PR China
b Department of Anatomy, Hebei United University at Qinhuangdao,
Qinhuangdao 066001, PR China
c Department of Pathophysiology, China Medical University, Shenyang
110001, PR China
Corresponding author. Tel./fax: +86 24 22529997.
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.
http://dx.doi.org/10.1016/j.neuint.2012.12.005
Who loves ya.
Tom
Jesus Was A Vegetarian!
http://tinyurl.com/2r2nkh
Man Is A Herbivore!
http://tinyurl.com/4rq595
DEAD PEOPLE WALKING
http://tinyurl.com/zk9fk
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