Web of Science: 77 cites, Scopus: 78 cites, Google Scholar: cites,
Deciphering the iron side of stroke : Neurodegeneration at the crossroads between iron dyshomeostasis, excitotoxicity, and ferroptosis
De Gregorio-Rocasolano, Nuria (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Martí-Sistac, O. (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Gasull Dalmau, Teresa (Institut Germans Trias i Pujol)

Data: 2019
Resum: In general, iron represents a double-edged sword in metabolism in most tissues, especially in the brain. Although the high metabolic demands of brain cells require iron as a redox-active metal for ATP-producing enzymes, the brain is highly vulnerable to the devastating consequences of excessive iron-induced oxidative stress and, as recently found, to ferroptosis as well. The blood-brain barrier (BBB) protects the brain from fluctuations in systemic iron. Under pathological conditions, especially in acute brain pathologies such as stroke, the BBB is disrupted, and iron pools from the blood gain sudden access to the brain parenchyma, which is crucial in mediating stroke-induced neurodegeneration. Each brain cell type reacts with changes in their expression of proteins involved in iron uptake, efflux, storage, and mobilization to preserve its internal iron homeostasis, with specific organelles such as mitochondria showing specialized responses. However, during ischemia, neurons are challenged with excess extracellular glutamate in the presence of high levels of extracellular iron; this causes glutamate receptor overactivation that boosts neuronal iron uptake and a subsequent overproduction of membrane peroxides. This glutamate-driven neuronal death can be attenuated by iron-chelating compounds or free radical scavenger molecules. Moreover, vascular wall rupture in hemorrhagic stroke results in the accumulation and lysis of iron-rich red blood cells at the brain parenchyma and the subsequent presence of hemoglobin and heme iron at the extracellular milieu, thereby contributing to iron-induced lipid peroxidation and cell death. This review summarizes recent progresses made in understanding the ferroptosis component underlying both ischemic and hemorrhagic stroke subtypes.
Ajuts: Agència de Gestió d'Ajuts Universitaris i de Recerca 2017SGR1520
Instituto de Salud Carlos III RD16-0019-0020
Nota: Altres ajuts: We acknowledge the funding received from "la Caixa" Foundation CI15-00009 and from the European Institute of Innovation and Technology (EIT) PoC-2016-SPAIN-04. EIT receives support from the European Union's Horizon 2020 research and innovation program.
Drets: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Llengua: Anglès
Document: Article de revisió ; Article ; Versió publicada
Matèria: Excitotoxicity ; Ferroptosis ; Iron ; Iron dyshomeostasis ; Neurodegeneration ; Reactive oxygen species ; Stroke ; Transferrin saturation
Publicat a: Frontiers in Neuroscience, Vol. 13 Núm. FEB (2019) , p. 85, ISSN 1662-453X

DOI: 10.3389/fnins.2019.00085
PMID: 30837827

17 p, 2.0 MB

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Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
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 Registre creat el 2020-06-03, darrera modificació el 2022-03-26

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