Deferoxamine inhibits iron induced hippocampal tau phosphorylation in the Alzheimer transgenic mouse brain

Guo, Chuangxin; Wang, Pu; Zhong, Manli; Wang, Tao; Huang, Xueshi; Li, Jiayi; Wang, Zhan-You

doi:10.1016/j.neuint.2012.12.005

Cited by 147 publications

(97 citation statements)

References 56 publications

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“…There is speculation that iron plays a large role in the pathophysiology of some common neurodegenerative disorders like Alzheimer's disease (AD), Parkinson's disease, Huntington's disease, and Neurochem Res amyotrophic lateral sclerosis [49]. Iron overload in rats enhances reactive oxygen species (ROS) [50], in brain regions such as the cerebral cortex and the hippocampus, areas known to be affected in AD [51]. Importantly, our previous studies exhibited that iron induced cholinergic deficits in the cerebral cortex in rats are protected by simultaneous treatment with naringenin [20].…”

Section: Discussionmentioning

confidence: 99%

Naringenin Mitigates Iron-Induced Anxiety-Like Behavioral Impairment, Mitochondrial Dysfunctions, Ectonucleotidases and Acetylcholinesterase Alteration Activities in Rat Hippocampus

et al. 2015

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Studies demonstrated that the iron chelating antioxidant restores brain dysfunction induced by iron toxicity in animals. Earlier, we found that iron overload-induced cerebral cortex apoptosis correlated with oxidative stress could be protected by naringenin (NGEN). In this respect, the present study is focused on the mechanisms associated with the protective efficacy of NGEN, natural flavonoid compound abundant in the peels of citrus fruit, on iron induced impairment of the anxiogenic-like behaviour, purinergic and cholinergic dysfunctions with oxidative stress related disorders on mitochondrial function in the rat hippocampus. Results showed that administration of NGEN (50 mg/kg/day) by gavage significantly ameliorated anxiogenic-like behaviour impairment induced by the exposure to 50 mg of Fe-dextran/kg/day intraperitoneally for 28 days in rats, decreased iron-induced reactive oxygen species formation and restored the iron-induced decrease of the acetylcholinesterase expression level, mitochondrial membrane potential and mitochondrial complexes activities in the hippocampus of rats. Moreover, NGEN was able to restore the alteration on the activity and expression of ectonucleotidases such as adenosine triphosphate diphosphohydrolase and 5'-nucleotidase, enzymes which hydrolyze and therefore control extracellular ATP and adenosine concentrations in the synaptic cleft. These results may contribute to a better understanding of the neuroprotective role of NGEN, emphasizing the influence of including this flavonoid in the diet for human health, possibly preventing brain injury associated with iron overload.

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Section: Discussionmentioning

confidence: 99%

Naringenin Mitigates Iron-Induced Anxiety-Like Behavioral Impairment, Mitochondrial Dysfunctions, Ectonucleotidases and Acetylcholinesterase Alteration Activities in Rat Hippocampus

et al. 2015

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“…In AD, increased iron co-localizes with insoluble tau tangles and facilitates the loss of soluble tau, further perturbating tau-mediate APP shuttling and ferroportin iron export 141,153 . The usage of iron chelators highlights this relationship as they decrease the phosphorylation of tau and its aggregation 45 . The loss of soluble tau prevents the tau stabilization of microtubules, altering molecular transport important for neurotransmission, synapse stability, and cellular health 158 .…”

Section: Neuronmentioning

confidence: 99%

“…Deferoxamine (DFO), a ferric iron chelator used to treat iron overload, has been shown to decrease tau phosphorylation, slow down amyloidogenesis, and improve behavioral impairment in an Alzheimer’s mouse and rabbit models 45–48 . DFO also improves behavioral performance in AD patients after a 24 month administration period 49 .…”

Section: Introductionmentioning

confidence: 99%

The relationship between iron dyshomeostasis and amyloidogenesis in Alzheimer's disease: Two sides of the same coin

Peters

Connor

Meadowcroft

2015

Neurobiology of Disease

120

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The dysregulation of iron metabolism in Alzheimer’s disease is not accounted for in the current framework of the amyloid cascade hypothesis. Accumulating evidence suggests that impaired iron homeostasis is an early event in Alzheimer’s disease progression. Iron dyshomeostasis leads to a loss of function in several enzymes requiring iron as a cofactor, the formation of toxic oxidative species, and the elevated production of beta-amyloid proteins. Several common genetic polymorphisms that cause increased iron levels and dyshomeostasis have been associated with Alzheimer’s disease but the pathoetiology is not well understood. A full picture is necessary to explain how heterogeneous circumstances lead to iron loading and amyloid deposition. There is evidence to support a causative interplay between the concerted loss of iron homeostasis and amyloid plaque formation. We hypothesize that iron misregulation and beta-amyloid plaque pathology are synergistic in the process of neurodegeneration and ultimately cause a downward cascade of events that spiral into the manifestation of Alzheimer’s disease. In this review, we amalgamate recent findings of brain iron metabolism in healthy versus Alzheimer’s disease brains and consider unique mechanisms of iron transport in different brain cells as well as how disturbances in iron regulation lead to disease etiology and propagate Alzheimer’s pathology.

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“…Indeed, iron interacts with hyperphosphorylated tau, an interaction that contributes to the formation of neurofibrillary tangles (Guo et al, 2013;Smith et al, 1997). Treatment of Fe 3+ -paired helical filament (PHF) aggregates from AD brains with the reducing agent β-mercaptoethanol results in solubilization of both reduced iron and PHFs, indicating that PHFs in association with Fe 3+ constitute the insoluble pool of PHFs (Yamamoto et al, 2002).…”

Section: Mitochondrial Dysfunction and Iron Accumulation In Admentioning

confidence: 99%

Mitochondrial iron homeostasis and its dysfunctions in neurodegenerative disorders

et al. 2015

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Deferoxamine inhibits iron induced hippocampal tau phosphorylation in the Alzheimer transgenic mouse brain

Cited by 147 publications

References 56 publications

Naringenin Mitigates Iron-Induced Anxiety-Like Behavioral Impairment, Mitochondrial Dysfunctions, Ectonucleotidases and Acetylcholinesterase Alteration Activities in Rat Hippocampus

Naringenin Mitigates Iron-Induced Anxiety-Like Behavioral Impairment, Mitochondrial Dysfunctions, Ectonucleotidases and Acetylcholinesterase Alteration Activities in Rat Hippocampus

The relationship between iron dyshomeostasis and amyloidogenesis in Alzheimer's disease: Two sides of the same coin

Mitochondrial iron homeostasis and its dysfunctions in neurodegenerative disorders

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