dc.creatorNúñez, Marco Tulio
dc.creatorHidalgo, Cecilia
dc.date.accessioned2019-10-22T03:11:13Z
dc.date.available2019-10-22T03:11:13Z
dc.date.created2019-10-22T03:11:13Z
dc.date.issued2019
dc.identifierFrontiers in Neuroscience, 12 February 2019
dc.identifier1662453X
dc.identifier16624548
dc.identifier10.3389/fnins.2019.00048
dc.identifierhttps://repositorio.uchile.cl/handle/2250/171889
dc.description.abstractIron and calcium share the common feature of being essential for normal neuronal function. Iron is required for mitochondrial function, synaptic plasticity, and the development of cognitive functions whereas cellular calcium signals mediate neurotransmitter exocytosis, axonal growth and synaptic plasticity, and control the expression of genes involved in learning and memory processes. Recent studies have revealed that cellular iron stimulates calcium signaling, leading to downstream activation of kinase cascades engaged in synaptic plasticity. The relationship between calcium and iron is Janus-faced, however. While under physiological conditions iron-mediated reactive oxygen species generation boosts normal calcium-dependent signaling pathways, excessive iron levels promote oxidative stress leading to the upsurge of unrestrained calcium signals that damage mitochondrial function, among other downstream targets. Similarly, increases in mitochondrial calcium to non-physiological levels result in mitochondrial dysfunction and a predicted loss of iron homeostasis. Hence, if uncontrolled, the iron/calcium self-feeding cycle becomes deleterious to neuronal function, leading eventually to neuronal death. Here, we review the multiple cell-damaging responses generated by the unregulated iron/calcium self-feeding cycle, such as excitotoxicity, free radical-mediated lipid peroxidation, and the oxidative modification of crucial components of iron and calcium homeostasis/signaling: the iron transporter DMT1, plasma membrane, and intracellular calcium channels and pumps. We discuss also how iron-induced dysregulation of mitochondrial calcium contributes to the generation of neurodegenerative conditions, including Alzheimer’s disease (AD) and Parkinson’s disease (PD).
dc.languageen
dc.publisherFrontiers Media
dc.rightshttp://creativecommons.org/licenses/by-nc-nd/3.0/cl/
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 Chile
dc.sourceFrontiers in Neuroscience
dc.subjectFerroptosis
dc.subjectHIF-1
dc.subjectInflammation
dc.subjectMitochondria
dc.subjectNeurodegenerative diseases
dc.subjectNrf-2
dc.subjectReactive oxygen species
dc.titleNoxious iron–calcium connections in neurodegeneration
dc.typeArtículo de revista


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