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  • Iron In Neurodegenerative Disease

    From ironjustice@21:1/5 to All on Mon Oct 1 15:58:27 2018
    Striking while the iron is hot: Iron metabolism and Ferroptosis in neurodegeneration.
    Masaldan S1, Bush AI2, Devos D3, Rolland AS4, Moreau C3.
    Free Radic Biol Med. 2018 Sep 25. pii: S0891-5849(18)31680-0. doi: 10.1016/j.freeradbiomed.2018.09.033. [Epub ahead of print]

    Abstract
    Perturbations in iron homeostasis and iron accumulation feature in several neurodegenerative disorders including Alzheimer's disease (AD), Parkinson's disease (PD) and Amyotrophic lateral sclerosis (ALS). Proteins such as α-synuclein, tau and amyloid
    precursor protein that are pathologically associated with neurodegeneration are involved in molecular crosstalk with iron homeostatic proteins. Quantitative susceptibility mapping, an MRI based non-invasive technique, offers proximal evaluations of iron
    load in regions of the brain and powerfully predicts cognitive decline. Further, small molecules that target elevated iron have shown promise against PD and AD in preclinical studies and clinical trials. Despite these strong links between altered iron
    homeostasis and neurodegeneration the molecular biology to describe the association between enhanced iron levels and neuron death, synaptic impairment and cognitive decline is ill defined. In this review we discuss the current understanding of brain iron
    homeostasis and how it may be perturbed under pathological conditions. Further, we explore the ramifications of a novel cell death pathway called ferroptosis that has provided a fresh impetus to the "metal hypothesis" of neurodegeneration. While lipid
    peroxidation plays a central role in the execution of this cell death modality the removal of iron through chelation or genetic modifications appears to extinguish the ferroptotic pathway. Conversely, tissues that harbour elevated iron may be predisposed
    to ferroptotic damage. These emerging findings are of relevance to neurodegeneration where ferroptotic signalling may offer new targets to mitigate cell death and dysfunction.

    KEYWORDS:
    Alzheimer's disease; Iron; Parkinson's disease; ferroptosis; neurodegeneration

    PMID: 30266679 DOI: 10.1016/j.freeradbiomed.2018.09.033

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