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Borchard, S. ; Raschke, S.* ; Zak, K.M. ; Eberhagen, C. ; Einer, C. ; Weber, E. ; Müller, S.M.* ; Michalke, B. ; Lichtmannegger, J. ; Wieser, A. ; Rieder, T.* ; Popowicz, G.M. ; Adamski, J. ; Klingenspor, M.* ; Coles, A.H.* ; Viana, R.* ; Vendelbo, M.H.* ; Sandahl, T.D.* ; Schwerdtle, T.* ; Plitz, T.* ; Zischka, H.

Bis-choline tetrathiomolybdate prevents copper-induced blood-brain barrier damage.

Life Sci. All. 5:e202101164 (2022)
Verlagsversion DOI
Open Access Gold
Creative Commons Lizenzvertrag
In Wilson disease, excessive copper accumulates in patients' livers and may, upon serum leakage, severely affect the brain according to current viewpoints. Present remedies aim at avoiding copper toxicity by chelation, for example, by D-penicillamine (DPA) or bis-choline tetrathiomolybdate (ALXN1840), the latter with a very high copper affinity. Hence, ALXN1840 may potentially avoid neurological deterioration that frequently occurs upon DPA treatment. As the etiology of such worsening is unclear, we reasoned that copper loosely bound to albumin, that is, mimicking a potential liver copper leakage into blood, may damage cells that constitute the blood-brain barrier, which was found to be the case in an in vitro model using primary porcine brain capillary endothelial cells. Such blood-brain barrier damage was avoided by ALXN1840, plausibly due to firm protein embedding of the chelator bound copper, but not by DPA. Mitochondrial protection was observed, a prerequisite for blood-brain barrier integrity. Thus, high-affinity copper chelators may minimize such deterioration in the treatment of neurologic Wilson disease.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Relative Exchangeable Copper; Wilson Disease Gene; Ammonium Tetrathiomolybdate; D-penicillamine; Rat Model; Serum; Zinc; Ceruloplasmin; Binding; Metal
ISSN (print) / ISBN 2575-1077
e-ISSN 2575-1077
Zeitschrift Life Science Alliance
Quellenangaben Band: 5, Heft: 3, Seiten: , Artikelnummer: e202101164 Supplement: ,
Verlag EMBO Press
Verlagsort Heidelberg
Begutachtungsstatus Peer reviewed
Förderungen Wilson Therapeutics AB/Alexion AstraZeneca Rare Disease
Morbus Wilson e.V.