Huntington’s Disease (HD) is another neurodegenerative disease. Different from AD, HD is an inherited disease caused by a genetic defect on chromosome 4, and the defect results in progressive breakdown (degeneration) of nerve cells in the brain. Symptoms of Huntington’s disease commonly become noticeable between the ages of 35 and 44 years.
Increasing evidences indicate that several epigenetic marks are altered in multiple HD models and in postmortem patient samples. Histone acetylation is the most studied epigenetic mark in cognition and neuropathology. For example, in HD models, depletion of soluble CBP is demonstrated to affect the transcriptional regulation of neuronal genes relevant to cell survival, and protein levels and nuclear distribution of class I and II HDACs also shows some alterations. Altered DNA methylation, implicated in a variety of neurodevelopmental disorders, are also examined, and the global levels of some CpG methylation, such as 7-methylguanine (7 mG) and 5 mG, are found to decrease in HD models.
Based on the epigenetic effects, related compounds, such as HDAC inhibitors and DNA methylation inhibitors, has been used in the therapy of HD. For example, SAHA and trichostatin A (TSA)) are both indicated to rescue degeneration and cell death in models of polyQ disorders. More details will be discussed in the future posts.