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Huntington's disease - Pongo abelii


Model information
Identifier: BMID000000016445
Format: SBML L3 V1 (Layout, Qualitative Models)
Project: path2models
Categories: non-metabolic
Submission: 17 May 2012 17:46:18 UTC
Last modified: 08 Dec 2012 01:17:57 UTC
Published: 20 May 2012 00:49:21 UTC
occursIn Pongo abelii Taxonomy
isDerivedFrom Huntington's disease KEGG Pathway
Model of “Huntington's disease” in “Pongo abelii (Sumatran orangutan)”
Huntington disease (HD) is an autosomal-dominant neurodegenerative disorder that primarily affects medium spiny striatal neurons (MSN). The symptoms are choreiform, involuntary movements, personality changes and dementia. HD is caused by a CAG repeat expansion in the IT15gene, which results in a long stretch of polyglutamine close to the amino-terminus of the HD protein huntingtin (Htt). Mutant Htt (mHtt) has effects both in the cytoplasm and in the nucleus. In the cytoplasm, full-length mHtt can interfere with BDNF vesicular transport on microtubules. This mutant protein also may lead to abnormal endocytosis and secretion in neurons, because normal Htt form a complex with the proteins Hip1, clathrin and AP2 that are involved in endocytosis. In addition, mHtt affects Ca2+ signaling by sensitizing InsP3R1 to activation by InsP3, stimulating NMDAR activity, and destabilizing mitochondrial Ca2+ handling. The mHtt translocates to the nucleus, where it forms intranuclear inclusions. Nuclear toxicity is believed to be caused by interference with gene transcription, leading to loss of transcription of neuroprotective molecules such as BDNF. While mHtt binds to p53 and upregulates levels of nuclear p53 as well as p53 transcriptional activity. Augmented p53 mediates mitochondrial dysfunction.

Graphical representation of 'Huntington's disease (Pongo abelii (Sumatran orangutan))'
(PNG image hosted by the Kyoto Encyclopedia of Genes and Genomes, KEGG).
This model has been automatically generated by KEGGtranslator V2.3.0 (KEGGtranslator: visualizing and converting the KEGG PATHWAY database to various formats. Wrzodek C, Dräger A, Zell A. Bioinformatics . 2011, 27 :2314-2315) using information coming from the KEGG PATHWAY Database ( original pathway ).
This model has been produced by the path2models project, it is currently hosted on BioModels Database and identified by: BMID000000016445 .
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.