Iron chelators inhibit amyloid-beta-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-beta-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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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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.

Original language	English
Article number	104607
Number of pages	4
Journal	Neurochemistry International
Volume	132
Early online date	21-Nov-2019
DOIs	https://doi.org/10.1016/j.neuint.2019.104607
Publication status	Published - Jan-2020

Keywords

Neutrophil gelatinase-associated lipocalin (NGAL)
Iron metabolism
Neuroinflammation
Ferritin
Deferoxamine
Deferiprone
UP-REGULATION
BRAIN-INJURY
INFLAMMATION
MICROGLIA
ACCUMULATION

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@article{4709f7e8c5eb415688f7d7241cde2f89,

title = "Iron chelators inhibit amyloid-beta-induced production of lipocalin 2 in cultured astrocytes",

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 = "Neutrophil gelatinase-associated lipocalin (NGAL), Iron metabolism, Neuroinflammation, Ferritin, Deferoxamine, Deferiprone, UP-REGULATION, BRAIN-INJURY, INFLAMMATION, MICROGLIA, ACCUMULATION",

author = "Dekens, {Doortje W} and {De Deyn}, {Peter P} and Friederike Sap and Eisel, {Ulrich L M} and Naud{\'e}, {Petrus J W}",

note = "Copyright {\textcopyright} 2019. Published by Elsevier Ltd.",

year = "2020",

month = jan,

doi = "10.1016/j.neuint.2019.104607",

language = "English",

volume = "132",

journal = "Neurochemistry International",

issn = "0197-0186",

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TY - JOUR

T1 - Iron chelators inhibit amyloid-beta-induced production of lipocalin 2 in cultured astrocytes

AU - Dekens, Doortje W

AU - De Deyn, Peter P

AU - Sap, Friederike

AU - Eisel, Ulrich L M

AU - Naudé, Petrus J W

PY - 2020/1

Y1 - 2020/1

N2 - 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.

AB - 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.

KW - Neutrophil gelatinase-associated lipocalin (NGAL)

KW - Iron metabolism

KW - Neuroinflammation

KW - Ferritin

KW - Deferoxamine

KW - Deferiprone

KW - UP-REGULATION

KW - BRAIN-INJURY

KW - INFLAMMATION

KW - MICROGLIA

KW - ACCUMULATION

U2 - 10.1016/j.neuint.2019.104607

DO - 10.1016/j.neuint.2019.104607

M3 - Article

C2 - 31760034

SN - 0197-0186

VL - 132

JO - Neurochemistry International

JF - Neurochemistry International

M1 - 104607

ER -