Noxious Iron-Calcium Connections in Neurodegeneration

Frontiers in Neuroscience
M T Núñez, C Hidalgo

Abstract

Iron 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 c...Continue Reading

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Citations

Oct 2, 2019·Frontiers in Aging Neuroscience·Matthew R HolahanFernando A Oliveira
Apr 9, 2020·Translational Neurodegeneration·Lu WangJian-Zhi Wang
May 28, 2020·International Journal of Molecular Sciences·Paolo SantambrogioSonia Levi
May 21, 2020·Mechanisms of Ageing and Development·Pablo MuñozYolanda Espinosa-Parrilla
Aug 31, 2021·Free Radical Biology & Medicine·Silvia GleitzeCecilia Hidalgo
Aug 4, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·Rachel NechushtaiRon Mittler

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