Genistein induces degradation of mutant huntingtin in fibroblasts from Huntington’s disease patients

Karolina Pierzynowska , Lidia Gaffke , Zuzanna Cyske , Grzegorz Węgrzyn


Mutations in the HTT gene, consisting of expansion of CAG triplets, cause the Huntington’s disease (HD), one of the major neurodegenerative disorders. Formation of aggregates of mutant huntingtin (mHTT, the product of the mutant HTT gene) leads to cellular dysfunctions, and subsequent neurodegeneration which manifest clinically as motor abnormalities and cognitive deficits. We recently used immortalized HEK-293 cells expressing the 1st exon of the mutant HTT gene as a cellular model of HD, and showed that the stimulation of autophagy by genistein corrected the mutant phenotype. However, effects of genistein on HD patient-derived cells remained unknown. In this report, we demonstrated that genistein also instigated degradation of mHTT in fibroblasts derived from HD patients. This was assessed as a significant decrease in the levels of HTT in HD fibroblasts measured by Western-blotting, and the disappearance of intracellular mHTT aggregates in cells observed by fluorescent microscopy. Fibroblasts derived from control persons were not affected by genistein treatment. These results indicate that genistein can improve HD phenotype in patient-derived cells, and substantiates the need for further studies of this isoflavone as a potential therapeutic agent.
Author Karolina Pierzynowska (FB / DMoB)
Karolina Pierzynowska,,
- Department of Molecular Biology
, Lidia Gaffke (FB / DMoB)
Lidia Gaffke,,
- Department of Molecular Biology
, Zuzanna Cyske (FB / DMoB)
Zuzanna Cyske,,
- Department of Molecular Biology
, Grzegorz Węgrzyn (FB / DMoB)
Grzegorz Węgrzyn,,
- Department of Molecular Biology
Journal seriesMetabolic Brain Disease, ISSN 0885-7490, e-ISSN 1573-7365, (N/A 70 pkt)
Issue year2019
Publication size in sheets0.5
Keywords in EnglishHuntington’s disease, genistein, huntingtin, protein degradation, protein aggregates, autophagy
ASJC Classification2728 Clinical Neurology; 1303 Biochemistry; 2804 Cellular and Molecular Neuroscience
Languageen angielski
LicenseOther; published final; Uznanie Autorstwa (CC-BY); with publication
Score (nominal)70
Score sourcejournalList
ScoreMinisterial score = 70.0, 28-01-2020, ArticleFromJournal
Publication indicators WoS Citations = 0; Scopus SNIP (Source Normalised Impact per Paper): 2016 = 0.798; WoS Impact Factor: 2018 = 2.411 (2) - 2018=2.548 (5)
Citation count*2 (2020-03-09)
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