Iron chelators inhibit amyloid-β-induced production of lipocalin 2 in cultured astrocytes

Doortje W Dekens; Peter P De Deyn; Friederike Sap; Ulrich L M Eisel; Petrus J W Naudé

doi:10.1016/j.neuint.2019.104607

Iron chelators inhibit amyloid-β-induced production of lipocalin 2 in cultured astrocytes

Neurochem Int. 2020 Jan:132:104607. doi: 10.1016/j.neuint.2019.104607. Epub 2019 Nov 21.

Authors

Doortje W Dekens¹, Peter P De Deyn², Friederike Sap³, Ulrich L M Eisel⁴, Petrus J W Naudé⁵

Affiliations

¹ Department of Neurology and Alzheimer Center Groningen, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, the Netherlands; Department of Molecular Neurobiology, Groningen Institute for Evolutionary Life Sciences (GELIFES), University of Groningen, Nijenborgh 7, 9747 AG, Groningen, the Netherlands. Electronic address: d.w.dekens@rug.nl.
² Department of Neurology and Alzheimer Center Groningen, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, the Netherlands; Laboratory of Neurochemistry and Behavior, Biobank, Institute Born-Bunge, University of Antwerp, Universiteitsplein 1, BE-2610, Antwerp, Belgium. Electronic address: p.p.de.deyn@umcg.nl.
³ Department of Molecular Neurobiology, Groningen Institute for Evolutionary Life Sciences (GELIFES), University of Groningen, Nijenborgh 7, 9747 AG, Groningen, the Netherlands. Electronic address: friederike.sap@web.de.
⁴ Department of Molecular Neurobiology, Groningen Institute for Evolutionary Life Sciences (GELIFES), University of Groningen, Nijenborgh 7, 9747 AG, Groningen, the Netherlands; University Center of Psychiatry & Interdisciplinary Center of Psychopathology of Emotion Regulation, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, the Netherlands. Electronic address: u.l.m.eisel@rug.nl.
⁵ Department of Neurology and Alzheimer Center Groningen, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, the Netherlands; Department of Molecular Neurobiology, Groningen Institute for Evolutionary Life Sciences (GELIFES), University of Groningen, Nijenborgh 7, 9747 AG, Groningen, the Netherlands. Electronic address: p.j.w.naude@umcg.nl.

PMID: 31760034
DOI: 10.1016/j.neuint.2019.104607

Abstract

Lipocalin 2 (Lcn2) has been implicated to play a role in various neurodegenerative diseases, and normalizing its overexpression may be of therapeutic potential. Iron chelators were found to reduce Lcn2 levels in certain animal models of CNS injury. Focusing on Alzheimer's disease (AD), we found that the iron chelators deferoxamine and deferiprone inhibited amyloid-β (Aβ)-induced Lcn2 production in cultured primary astrocytes. Accordingly, Aβ-exposure increased astrocytic ferritin production, indicating the possibility that Aβ induces iron accumulation in astrocytes. This effect was not significantly modulated by Lcn2. Known neuroprotective effects of iron chelators may rely in part on normalization of Lcn2 levels.

Keywords: Deferiprone; Deferoxamine; Ferritin; Iron metabolism; Neuroinflammation; Neutrophil gelatinase-associated lipocalin (NGAL).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amyloid beta-Peptides / toxicity*
Animals
Animals, Newborn
Astrocytes / drug effects*
Astrocytes / metabolism*
Cells, Cultured
Dose-Response Relationship, Drug
Humans
Iron Chelating Agents / pharmacology*
Lipocalin-2 / antagonists & inhibitors*
Lipocalin-2 / biosynthesis*
Mice
Mice, Knockout
Peptide Fragments / toxicity*

Substances

Amyloid beta-Peptides
Iron Chelating Agents
Lipocalin-2
Peptide Fragments
amyloid beta-protein (1-42)
Lcn2 protein, mouse