Topoisomerase 1 (TOP1) conditionally deleted neurons develop properly but then show biased transcriptional downregulation of long genes signs of DNA damage neuroinflammation increased poly(ADP-ribose) polymerase-1 (PARP1) activity single-cell somatic mutations and ultimately degeneration. While neurodegeneration is partially rescued by supplementations behavioral decline is not prevented.
this study identified topoisomerase 1 as a cardinal Aire partner that colocalized on super-enhancers and was required for the interaction of Aire with all of its other associates
treatment of topotecan a brain-penetrating topoisomerase 1 inhibitor to HD transgenic mouse considerably improved its motor behavioural abnormalities. Finally we show that topotecan treatment to HD mouse not only inhibits the expression of transgenic mutant huntingtin but also at the same time induces the expression of Ube3a
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