Huntington’s Disease (HD) is a fatal, progressing neurodegenerative disorder that is the result of a genetic mutation in the Huntingtin gene causing synthesis of a mutated huntingtin (Htt) protein. Symptoms most frequently associated with this disease are movement disorders, including impaired motor function, behavioral modification and cognitive impairment that ultimately results in dementia. It has been observed in animal models that HD subjects had diminished CBP activity and decreased neuronal histone acetylation.

• Valor LM, Viosca J, Lopez-Atalaya JP, Barco A (2013-07-31). “Lysine acetyltransferases CBP and p300 as therapeutic targets in cognitive and neurodegenerative disorders”. Current Pharmaceutical Design. 19 (28): 5051–5064. doi:10.2174/13816128113199990382. PMC 3722569. PMID 23448461.
• Kim C, Yousefian-Jazi A, Choi SH, Chang I, Lee J, Ryu H (November 2021). “Non-Cell Autonomous and Epigenetic Mechanisms of Huntington’s Disease”. International Journal of Molecular Sciences. 22 (22): 12499. doi:10.3390/ijms222212499. PMC 8617801. PMID 34830381.

Research has shown that mutHtt directly interacts with CBP It has been hypothesized that mutant Htt is either capable of degrading CBP, or it directly inhibits CBP’s acetyltransferase domain.

• Valor LM, Viosca J, Lopez-Atalaya JP, Barco A (2013-07-31). “Lysine acetyltransferases CBP and p300 as therapeutic targets in cognitive and neurodegenerative disorders”. Current Pharmaceutical Design. 19 (28): 5051–5064. doi:10.2174/13816128113199990382. PMC 3722569. PMID 23448461.
•  Rouaux C, Loeffler JP, Boutillier AL (September 2004). “Targeting CREB-binding protein (CBP) loss of function as a therapeutic strategy in neurological disorders”. Biochemical Pharmacology. 68 (6): 1157–1164. doi:10.1016/j.bcp.2004.05.035. PMID 15313413.