March, Michael E.Gutiérrez Uzquiza, ÁlvaroSnorradottir, Asbjorg OskMatsuoka, Leticia S.Fonseca Balvis, NoeliaGestsson, ThorgeirNguyen, KennySleiman, Patrick M. A.Kao, CharllyIsaksson, Helgi JBragason, Birkir ThorOlafsson, EliasPalsdottir, AstridurHakonarson, Hakon2025-01-212025-01-212021-03-23March 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/s41467-021-22120-42041-172310.1038/s41467-021-22120-4https://hdl.handle.net/20.500.14352/115287Hereditary 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.engAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/journal articlehttps://doi.org/10.1038/s41467-021-22120-4open access577.1Bioquímica (Farmacia)Biología molecular (Farmacia)Neurociencias (Farmacia)2403 Bioquímica