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The epigenome is compromised in Huntington’s disease

58 months
Approved budget:
Dr Pritika Narayan
Health issue:
Neurological (CNS)
Proposal type:
Emerging Researcher First Grant
Lay summary
Huntington’s disease (HD) is a devastating neurodegenerative disorder caused by a genetic mutation in the huntingtin gene. The mutation encodes an expanded stretch of glutamine amino acids in the huntingtin protein, which significantly alters its shape and function. Preliminary results provide compelling evidence that histone modifications become dysregulated in HD. Histone modifications come under the umbrella of epigenetics (molecular interactions that allow communication between genes and the environment). Healthy cells maintain tightly regulated epigenetic-driven responses to environmental stress. However if this interface becomes compromised, as postulated here for HD, the cellular response to stress could be fatal. This research proposal hypothesises that the mutant huntingtin protein aberrantly interacts with enzymes that regulate the epigenome causing a progressive defect in epigenetic-driven cellular responses to stress. Developing ways to manipulate and restore the epigenome could give rise to novel therapeutic strategies for the treatment of HD.