Dataset: Expression data from WT and R6/2 mice treated with HSP90 inhibitor NVP-HSP990

[u'Huntington\u2019s disease (HD) is a neurodegenerative disorder that is associated with the deposition of proteinaceous aggregates in the brains of HD patients and mouse models. Previous studies have suggested that wide-scale disruption of protein homeostasis occurs in protein folding diseases. Protein homeostasis can be maintained by activation of the heat shock response (HSR) via the transcription factor heat shock factor 1 (HSF1), the pharmacological activation of which can be achieved by Hsp90 inhibition and has been demonstrated to be beneficial in cell and invertebrate models of HD. Whether the HSR is functional in HD and whether its activation has therapeutic potential in mammalian HD models is currently unknown. To address these issues, we used a novel, brain penetrant Hsp90 inhibitor to activate the HSR in brain after systemic administration. Microarrays, quantitative PCR and western blotting showed that the HSR becomes impaired with disease progression in two mouse models of HD and that this originates at the level of transcription. Huntington\u2019s disease (HD) is a neurodegenerative disorder that is associated with the deposition of proteinaceous aggregates in the brains of HD patients and mouse models. Previous studies have suggested that wide-scale disruption of protein homeostasis occurs in protein folding diseases. Protein homeostasis can be maintained by activation of the heat shock response (HSR) via the transcription factor heat shock factor 1 (HSF1), the pharmacological activation of which can be achieved by Hsp90 inhibition and has been demonstrated to be beneficial in cell and invertebrate models of HD. Whether the HSR is functional in HD and whether its activation has therapeutic potential in mammalian HD models is currently unknown. To address these issues, we used a novel, brain penetrant Hsp90 inhibitor to activate the HSR in brain after systemic administration. Microarrays, quantitative PCR and western blotting showed that the HSR becomes impaired with disease progression in two mouse models of HD and that this originates at the level of transcription. mRNA expression analysis was performed by microarray in 12 week old R6/2 and WT mice treated with vehicle or HSP990 for 4h (12mg/kg).The following number of replicates was analysed for each genotype: 7 for WT+vehicle, 10 for WT+HSP990, 7 for R6/2+vehicle and 8 for R6/2+HSP990. Microarray quality control was performed using the software package provided on RACE (', {u'a': {u'href': u'http://race.unil.ch', u'target': u'_blank', u'$': u'http://race.unil.ch'}}, u').']

Species:

mouse

Samples:

32

Source:

E-GEOD-29681

Updated:

Dec.12, 2014

Registered:

Nov.11, 2014