Brain iron metabolism: Neurobiology and neurochemistry

Ke, Ya; Qian, Zhong Ming

doi:10.1016/j.pneurobio.2007.07.009

Cited by 217 publications

(179 citation statements)

References 345 publications

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“…Thus, levels of iron and iron-modulating proteins in the serum and cerebrospinal fluid (CSF) that bathe the brain differ significantly (311 (210), and captured by circulating Tf in the brain interstitial fluid and CSF. A significant amount of transported iron circulates in association with citrate, ascorbate, or ATP (224,286). Brain Tf is secreted by cells of the choroid plexus and oligodendrocytes, though participation of the latter is controversial.…”

Section: Iron Homeostasis Within the Brain And Regulation At Thementioning

confidence: 99%

“…The brain acquires iron from the systemic circulation through a tightly controlled mechanism at the blood brain barrier (BBB). Within the brain, iron serves essential functions that are best exemplified by brain disorders which arise from iron deficiency, excess, or mis-metabolism (97,224,312,413). Table 1 provides a partial list of human disorders that result from dysfunction or absence of one or more proteins involved in brain iron metabolism, and representative animal models.…”

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confidence: 99%

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Brain Iron Homeostasis: From Molecular Mechanisms To Clinical Significance and Therapeutic Opportunities

Singh

Haldar

Tripathi

et al. 2014

Antioxidants & Redox Signaling

176

165

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Iron has emerged as a significant cause of neurotoxicity in several neurodegenerative conditions, including Alzheimer's disease (AD), Parkinson's disease (PD), sporadic Creutzfeldt-Jakob disease (sCJD), and others. In some cases, the underlying cause of iron mis-metabolism is known, while in others, our understanding is, at best, incomplete. Recent evidence implicating key proteins involved in the pathogenesis of AD, PD, and sCJD in cellular iron metabolism suggests that imbalance of brain iron homeostasis associated with these disorders is a direct consequence of disease pathogenesis. A complete understanding of the molecular events leading to this phenotype is lacking partly because of the complex regulation of iron homeostasis within the brain. Since systemic organs and the brain share several iron regulatory mechanisms and iron-modulating proteins, dysfunction of a specific pathway or selective absence of iron-modulating protein(s) in systemic organs has provided important insights into the maintenance of iron homeostasis within the brain. Here, we review recent information on the regulation of iron uptake and utilization in systemic organs and within the complex environment of the brain, with particular emphasis on the underlying mechanisms leading to brain iron mismetabolism in specific neurodegenerative conditions. Mouse models that have been instrumental in understanding systemic and brain disorders associated with iron mis-metabolism are also described, followed by current therapeutic strategies which are aimed at restoring brain iron homeostasis in different neurodegenerative conditions. We conclude by highlighting important gaps in our understanding of brain iron metabolism and mis-metabolism, particularly in the context of neurodegenerative disorders. Antioxid. Redox Signal. 20, 1324Signal. 20, -1363

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Section: Iron Homeostasis Within the Brain And Regulation At Thementioning

confidence: 99%

mentioning

confidence: 99%

Brain Iron Homeostasis: From Molecular Mechanisms To Clinical Significance and Therapeutic Opportunities

Singh

Haldar

Tripathi

et al. 2014

Antioxidants & Redox Signaling

176

165

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“…In this pool, iron is redox-active and a cellular source that is available for iron metabolism regulation [60,61] . Iron regulatory protein-1 (IRP-1) functions as an mRNA-binding protein or as an aconitase depending on whether it disassembles or assembles ironsulfur clusters in response to iron deficiency and abundance, respectively [62][63][64][65] . TfR1 and DMT1 are two major iron uptake proteins with iron-responsive elements (IREs) in their 3'-untranslated regions and are regulated by IRE/IRP [65] .…”

Section: Discussionmentioning

confidence: 99%

Acetylcholinesterase-independent protective effects of huperzine A against iron overload-induced oxidative damage and aberrant iron metabolism signaling in rat cortical neurons

et al. 2016

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Aim: Iron dyshomeostasis is one of the primary causes of neuronal death in Alzheimer's disease (AD). Huperzine A (HupA), a natural inhibitor of acetylcholinesterase (AChE), is a licensed anti-AD drug in China and a nutraceutical in the United Sates. Here, we investigated the protective effects of HupA against iron overload-induced injury in neurons. Methods: Rat cortical neurons were treated with ferric ammonium citrate (FAC), and cell viability was assessed with MTT assays. Reactive oxygen species (ROS) assays and adenosine triphosphate (ATP) assays were performed to assess mitochondrial function. The labile iron pool (LIP) level, cytosolic-aconitase (c-aconitase) activity and iron uptake protein expression were measured to determine iron metabolism changes. The modified Ellman's method was used to evaluate AChE activity. Results: HupA significantly attenuated the iron overload-induced decrease in neuronal cell viability. This neuroprotective effect of HupA occurred concurrently with a decrease in ROS and an increase in ATP. Moreover, HupA treatment significantly blocked the upregulation of the LIP level and other aberrant iron metabolism changes induced by iron overload. Additionally, another specific AChE inhibitor, donepezil (Don), at a concentration that caused AChE inhibition equivalent to that of HupA negatively, influenced the aberrant changes in ROS, ATP or LIP that were induced by excessive iron. Conclusion: We provide the first demonstration of the protective effects of HupA against iron overload-induced neuronal damage. This beneficial role of HupA may be attributed to its attenuation of oxidative stress and mitochondrial dysfunction and elevation of LIP, and these effects are not associated with its AChE-inhibiting effect.

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“…O Fe, um metal redox-ativo, é o elemento de transição mais abundante em sistemas vivos. No entanto, uma das desordens genéticas mais prevalentes em humanos é causada por sobrecarga de Fe no organismo (hemocromatose hereditária) [5]. Desta forma o Fe é particularmente nocivo quando em excesso ou pobremente compartimentalizado.…”

Section: Ferrioxamina Bunclassified

Simulações computacionais de moléculas com aplicações em biociências

Suárez¹

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AgradecimentosOs meus sinceros agradecimentos À minha orientadora, Professora Helena Maria Petrilli, agradeço pela confiança depositada em mim, pela atenção e paciência que sempre teve e pelos sábios conselhos que com certeza vou levar comigo. À Prof. Dra. Lucy Vitória Credido Assali, Prof. Luis Gregório Dias e família pela ajuda em momentos delicados.Ao Prof. Dr. Breno Pannia Espósito, Prof. Vera R. Leopoldo Constantino e seu grupo de pesquisa do IQ, pela ajuda ao tratar e entender a Química envolvida neste presente trabalho. Agradecimentos especiais para o meus amigos Philippe Petersen, Arles Gil Rebaza e FilipeDalmatti por ter me ajudado muito para que este trabalho fosse realizado. A Sandra e Família, por serem pessoas muito boas e terem tido muita paciência comigo. À Rosana, pela sua calma e prontidão para resolver os problemas. À Adriana Rocio Cárdenas Arias, por seu amor e por ser a pessoa que mais me incentivou e me ajudou nos momentos difíceis.À meus pais René Diaz Barroso e Norma Suarez Cruz por ajudar a realizar meus sonhos. AbstractIn the present work we performed electronic structure calculations within the Kohn-Sham scheme of the density functional theory (DFT). We studied two molecules with potential applications in life sciences and medicine: ferrioxamine B and 5,10,15,23H (TMPyP) porphyrin. We used different methods and different exchange and correlation functionals, analyzing optical and vibrational properties and hyperfine interactions. In the case of ferrioxamine B, results in the crystalline phase (molecular crystal), and gas phase were compared with experimental results obtained using Mössbauer spectroscopy from the literature. We analyzed hyperfine parameters such as the electric quadrupole splitting, asymmetry parameter, hyperfine field and isomer shift. In the case of TMPyP porphyrin we analyzed vibrational properties in the gas phase and optical properties. For the electronic absorption, solvent effects and electronic charges states were analyzed. X XI

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Brain iron metabolism: Neurobiology and neurochemistry

Cited by 217 publications

References 345 publications

Brain Iron Homeostasis: From Molecular Mechanisms To Clinical Significance and Therapeutic Opportunities

Brain Iron Homeostasis: From Molecular Mechanisms To Clinical Significance and Therapeutic Opportunities

Acetylcholinesterase-independent protective effects of huperzine A against iron overload-induced oxidative damage and aberrant iron metabolism signaling in rat cortical neurons

Simulações computacionais de moléculas com aplicações em biociências

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