Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8842208 | Progress in Neurobiology | 2017 | 51 Pages |
Abstract
Although aberrant metabolism and deposition of iron has been associated with aging and neurodegeneration, the contribution of iron to neuropathology is unclear. Well-designed model systems that are suited to studying the putative pathological effect of iron are likely to be essential if such unresolved details are to be clarified. In this review, we have evaluated the utility and effectiveness of the reductionist in vitro platform to study the molecular mechanisms putatively underlying iron perturbations of neurodegenerative disease. The expression and function of iron metabolism proteins in glia and neurons and the extent to which this iron regulatory system is replicated in in vitro models has been comprehensively described, followed by an appraisal of the inherent suitability of different in vitro and ex vivo models that have been, or might be, used for iron loading. Next, we have identified and critiqued the relevant experimental parameters that have been used in in vitro iron loading experiments, including the choice of iron reagent, relevant iron loading concentrations and supplementation with serum or ascorbate, and propose optimal iron loading conditions. Finally, we have provided a synthesis of the differential iron accumulation and toxicity in glia and neurons from reported iron loading paradigms. In summary, this review has amalgamated the findings and paradigms of the published reports modelling iron loading in monocultures, discussed the limitations and discrepancies of such work to critically propose a robust, relevant and reliable model of iron loading to be used for future investigations.
Keywords
Fe-NTALFRAFUAPPSynchrotron X-ray fluorescenceHEPHIrp2hEPCFTHFTLDMT1MtFPYRFPNferroportinNTBIduodenal cytochrome BDcytBTFRLIPSXRFHcp1HO-1AASFAS27-OHCLA-ICP-MSOSCTim-2IRP1FACOPCsAscorbateFerric Ammonium CitrateBrain ironIron regulatory protein 2Labile iron poolAlzheimer’s diseaseCHOPFerritin Heavy ChainFerritin Light ChainSerumOligodendrocyte precursor cellsFerrous sulfateAtomic absorption spectroscopyLaser ablation inductively coupled plasma mass spectrometryNon-transferrin bound ironOrganotypic slice culturesferrocenemitochondrial ferritinFerric citrateLactoferrinCSFCerebrospinal fluidDivalent metal transporter 1Iron toxicityIron quantificationMelanotransferrinUTR یا untranslated regions untranslated regionHepcidinIron regulatory protein 1Iron regulatory proteinsamyloid precursor proteinPyrithioneChoroid plexusferric chlorideFerrous chloridetransferrin receptorLactoferrin Receptor
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Authors
Sinead Healy, Jill M. McMahon, Una FitzGerald,