Accepted_test

Effect of PARP1 inhibitor on expression of genes associated with Huntington's disease in differentiated iPSC derivatives

by Vladlena Makeeva | Institute of Cytology and Genetics SB RAS

Abstract ID: 796

Event: BGRS-abstracts

Sections: [Sym 9] Section “Gene and genome editing in modeling human pathological disease processes”

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by the expansion of CAG codons in the first exon of the HTT gene and leading to dysfunction and death of medium spiny neurons in the striatum of the brain of patients. Some of the causes of pathogenesis are disruption of energy homeostasis, development of ER stress and dysfunction of a number of transcription factors. Hyperactivation of the PARP1 repair enzyme as a result of chronic DNA damage makes a major contribution to these disorders. Testing a PARP inhibitor on a mouse model of Huntington's disease has shown a decrease in the rate of disease development, so the next step we decided to test the drug on a human model. For this purpose, we obtained medium spiny neuron lines with expression of the ER stress sensor based on iPSCs from a patient with HD and analyzed changes in gene expression, changes in the expression of which are associated with the development of HD.