Iron chelators inhibit amyloid-β-induced production of lipocalin 2 in cultured astrocytes. (January 2020)

• Record Type: Journal Article
• Authors: Dekens, Doortje W.; De Deyn, Peter P.; Sap, Friederike; Eisel, Ulrich L.M.; Naudé, Petrus J.W.
• Is Part Of: Neurochemistry international. Volume 132(2020)
• Publication Date: 2020-01
• Subjects: Neutrophil gelatinase-associated lipocalin (NGAL) -- Iron metabolism -- Neuroinflammation -- Ferritin -- Deferoxamine -- Deferiprone; Neurochemistry -- Periodicals; Neurochemistry -- Periodicals; Neurochimie -- Périodiques; Neurochemistry; Periodicals; 612.804205
• DOI: 10.1016/j.neuint.2019.104607
• Languages: English
• ISSNs: 0197-0186

Abstract

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. Highlights: Amyloid-β (Aβ) induces Lipocalin 2 (Lcn2) production in primary cultured astrocytes. Iron chelators deferoxamine and deferiprone abrogate Aβ-induced Lcn2 production. Aβ affects iron homeostasis in primary astrocyte cultures. Lcn2 is not essential for Aβ-induced disturbance of astrocytic iron homeostasis.