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

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

Publication date: Mar 09, 2019

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.

Pierzynowska, K., Gaffke, L., Cyske, Z., and Wegrzyn, G. Genistein induces degradation of mutant huntingtin in fibroblasts from Huntington’s disease patients. 06390. 2019 Metab Brain Dis.

Concepts Keywords
Autophagy HD
Cognitive Fibroblast
Exon Neurodegeneration
Fibroblasts MTOR
Fluorescent Microscopy HTT
Gene Genistein
Genistein Autophagy
HEK Huntington’s disease
Huntingtin Huntingtin
Huntington Branches of biology
Intracellular
Isoflavone
Mutant
Neurodegeneration
Neurodegenerative Disorders
Phenotype
Western Blotting

Semantics

Type Source Name
gene UNIPROT HTT
drug DRUGBANK Genistein
drug DRUGBANK Isoflavone
gene UNIPROT EPHA3
disease MESH abnormalities
gene UNIPROT SLC6A4
disease MESH neurodegenerative disorders

Original Article

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