RT Journal Article
T1 NAC blocks Cystatin C amyloid complex aggregation in a cell system and in skin of HCCAA patients
A1 March, Michael E.
A1 Gutiérrez Uzquiza, Álvaro
A1 Snorradottir, Asbjorg Osk
A1 Matsuoka, Leticia S.
A1 Fonseca Balvis, Noelia
A1 Gestsson, Thorgeir
A1 Nguyen, Kenny
A1 Sleiman, Patrick M. A.
A1 Kao, Charlly
A1 Isaksson, Helgi J
A1 Bragason, Birkir Thor
A1 Olafsson, Elias
A1 Palsdottir, Astridur
A1 Hakonarson, Hakon
AB Hereditary cystatin C amyloid angiopathy is a dominantly inherited disease caused by a leucine to glutamine variant of human cystatin C (hCC). L68Q-hCC forms amyloid deposits in brain arteries associated with micro-infarcts, leading ultimately to paralysis, dementia and death in young adults. To evaluate the ability of molecules to interfere with aggregation of hCC while informing about cellular toxicity, we generated cells that produce and secrete WT and L68Q-hCC and have detected high-molecular weight complexes formed from the mutant protein. Incubations of either lysate or supernatant containing L68Q-hCC with reducing agents glutathione or N-acetyl-cysteine (NAC) breaks oligomers into monomers. Six L68QhCC carriers taking NAC had skin biopsies obtained to determine if hCC deposits were reduced following NAC treatment. Remarkably, ~50–90% reduction of L68Q-hCC staining was observed in five of the treated carriers suggesting that L68Q-hCC is a clinical target for reducing agents.
SN 2041-1723
YR 2021
FD 2021-03-23
LK https://hdl.handle.net/20.500.14352/115287
UL https://hdl.handle.net/20.500.14352/115287
LA eng
NO March ME, Gutierrez-Uzquiza A, Snorradottir AO, Matsuoka LS, Balvis NF, Gestsson T, et al. NAC blocks Cystatin C amyloid complex aggregation in a cell system and in skin of HCCAA patients. Nat Commun [Internet]. 23 de marzo de 2021 [citado 21 de enero de 2025];12(1):1827. Disponible en: https://www.nature.com/articles/s41467-021-22120-4
NO Institutional Development Fund to the Center for Applied Genomics from Children’s Hospital of Philadelphia
DS Docta Complutense
RD 6 may 2025