RT Journal Article
SR Electronic
T1 Bis-choline tetrathiomolybdate prevents copper-induced blood–brain barrier damage
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202101164
DO 10.26508/lsa.202101164
VO 5
IS 3
A1 Borchard, Sabine
A1 Raschke, Stefanie
A1 Zak, Krzysztof M
A1 Eberhagen, Carola
A1 Einer, Claudia
A1 Weber, Elisabeth
A1 Müller, Sandra M
A1 Michalke, Bernhard
A1 Lichtmannegger, Josef
A1 Wieser, Albrecht
A1 Rieder, Tamara
A1 Popowicz, Grzegorz M
A1 Adamski, Jerzy
A1 Klingenspor, Martin
A1 Coles, Andrew H
A1 Viana, Ruth
A1 Vendelbo, Mikkel H
A1 Sandahl, Thomas D
A1 Schwerdtle, Tanja
A1 Plitz, Thomas
A1 Zischka, Hans
YR 2022
UL http://www.life-science-alliance.org/content/5/3/e202101164.abstract
AB 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.