Preferred Label : Inhibition of Huntington's Disease Pathway;
NCIt synonyms : Inhibition of Huntingtons Disease Pathway;
NCIt related terms : Inhibition of Huntington's disease neurodegeneration by histone deacetylase inhibitors;
Alternative definition : BIOCARTA: Huntington's disease is a neurodegenerative condition caused by a dominant
mutation in a gene encoding a protein now called huntingtin. Large polyglutamine repeats
in the huntingtin protein are the genetic defect responsible for this condition, caused
by expansion of a three-base pair repeat in the gene. Similar expansions of polyglutamine
repeats are also found in other genes involved in neurodegenerative conditions. The
polyglutamine repeat makes huntingtin protein insoluble and triggers the formation
of protein aggregates. There are a few hypotheses for the connection between these
aggregates and the neurodegeneration observed in Huntington's disease. One hypothesis
is that mutant huntingtin moves into the nucleus and interferes with transcriptional
activation involving the transcriptional coactivator CBP (CREB binding protein) and
other coactivators. CBP interacts with transcriptional regulatory factors and with
the basal transcriptional machinery to help regulate transcription. CBP is a large
protein with multiple domains and in addition to interacting with several different
transcription factors also has a histone acetylase enzyme activity. Mutant huntingtin
binds to CBP, drawing it into insoluble protein aggregates. Mutant huntingtin also
interacts directly with the acetyltransferase domain of CBP, blocking this activity.
Activation of CBP acetyltransferase activity by transcriptional regulators results
in the acetylation of histones in the promoter and enhancer regions of active genes,
contributing to transcriptional activation by making these genes more accessible in
chromatin. The lack of CBP in Huntington's affected neurons may lead to transcriptional
repression of key genes that in turn leads to neurodegeneration. One potential treatment
being tested is the treatment of Huntington's affected individuals with histone deacetylase
inhibitors to restore normal acetylation levels and transcription. The repression
of transcription may also be involved in other neurodegenerative conditions caused
by proteins with expansions of polyglutamine repeats. (This definition may be outdated
- see the DesignNote.);
NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by
BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus
staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA
Definition might be outdated or inaccurate. Please see the Terms and Conditions for
Use at http://www.biocarta.com/.;
Biocarta ID : h_HuntingtonPathway;
Origin ID : C39110;
UMLS CUI : C1512775;
Semantic type(s)
- has_gene_product_element
- pathway_has_gene_element
