Deciphering the Iron Side of Stroke: Neurodegeneration at the Crossroads Between Iron Dyshomeostasis, Excitotoxicity, and Ferroptosis.
DeGregorio-Rocasolano N1, MartÃ-Sistac O1,2, Gasull T1.
Front Neurosci. 2019 Feb 19;13:85. doi: 10.3389/fnins.2019.00085. eCollection 2019.
1
Cellular and Molecular Neurobiology Research Group, Department of Neurosciences, Germans Trias i Pujol Research Institute (IGTP), Badalona, Spain.
2
Department of Cellular Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Bellaterra, Spain.
Abstract
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.
KEYWORDS:
excitotoxicity; ferroptosis; iron; iron dyshomeostasis; neurodegeneration; reactive oxygen species; stroke; transferrin saturation
PMID: 30837827 PMCID: PMC6389709 DOI: 10.3389/fnins.2019.00085
Who loves ya.
Tom
Jesus Was A Vegetarian!
http://tinyurl.com/2r2nkh
Man Is A Herbivore!
http://tinyurl.com/4rq595
DEAD PEOPLE WALKING
http://tinyurl.com/zk9fk
--- SoupGate-Win32 v1.05
* Origin: fsxNet Usenet Gateway (21:1/5)