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Maheshwari, M and Bhutani, S and Das, A and Mukherjee, R and Sharma, A and Kino, Y and Nukina, N and Jana, NR (2014) Dexamethasone induces heat shock response and slows down disease progression in mouse and fly models of Huntington's disease. Hum Mol Genet., 23 (10). pp. 2737-2751.

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Huntington's disease (HD) is an inherited neurodegenerative disorder caused by abnormal expansion of glutamine repeats in the protein huntingtin. In HD brain, mutant huntingtin undergoes proteolytic processing, and its N-terminal fragment containing poly-glutamine repeats accumulate as insoluble aggregates leading to the defect in cellular protein quality control system and heat shock response (HSR). Here we demonstrate that the defective HSR in the brain is due to the down-regulation of heat shock factor 1 (HSF1) in both mice and fly models of HD. Interestingly, treatment of dexamethasone (a synthetic glucocorticoid) to HD mice or flies significantly increased the expression and transactivation of HSF1 and induction of HSR and these effects are mediated through the down-regulation of HSP90. Dexamethasone treatment also significantly decreased the aggregate load and transient recovery of HD-related behavioural phenotypes in both disease models. These results suggest that dexamethasone could be a potential therapeutic molecule for the treatment of HD and related poly-glutamine disorders.

Item Type: Article
Subjects: Neurodegenerative Disorders
Neuro-Oncological Disorders
Neurocognitive Processes
Neuronal Development and Regeneration
Informatics and Imaging
Genetics and Molecular Biology
Depositing User: Mr D.D. Lal
Date Deposited: 07 Jul 2017 05:03
Last Modified: 08 Aug 2017 05:22
URI: http://nbrc.sciencecentral.in/id/eprint/154

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