| Registro completo |
| Provedor de dados: |
Nature Precedings
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| País: |
United Kingdom
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| Título: |
A Systems Biology Approach towards Deciphering the Unfolded Protein Response in Huntington's Disease
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| Autores: |
Kameshwar R. Ayasolla
Ravi K. R. Kalathur
Matthias E. Futschik
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| Data: |
2012-04-01
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| Ano: |
2012
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| Palavras-chave: |
Neuroscience
Bioinformatics
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| Resumo: |
Although the disease causing gene huntingtin has been known for some time, the exact cause of neuronal cell death during _Huntington's disease_ (HD) remains unknown. One potential mechanism contributing to the massive loss of neurons in HD brains might be the _Unfolded Protein Response_ (UPR) which is activated by accumulation of misfolded proteins in the endoplasmic reticulum (ER). As an adaptive response, UPR upregulates transcription of chaperones, temporarily attenuating new translation and activates protein degradation via the proteasome. However, at high levels of ER stress, UPR signalling can contribute to neuronal apoptosis.

Our primary aims include (a) construction of the UPR signalling network, (b) curation and bioinformatical identification of UPR target genes and finally (c) examination of HD gene expression data sets for UPR transcriptional signatures and differential regulation of UPR pathways.

The UPR signalling pathway is reconstructed based on literature review and using the "Unified Interactome database":http://www.unihi.org. Lists of UPR target genes detected by previous experiments or as predicted by computational analysis are compiled. This allows us to perform enrichment analysis for differential HD gene expression and to assess whether UPR expression signatures are prominent during HD pathogenesis.

Results: The canonical UPR pathway is complemented with additional protein interaction data allowing us to assess its embedding into the cellular context and to identify potential modifiers as well as novel drug targets.

Conclusions: The in depth systems biology analysis can give us valuable insights about the involvement of the UPR in HD.

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| Tipo: |
Poster
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| Identificador: |
http://precedings.nature.com/documents/7078/version/1
oai:nature.com:10.1038/npre.2012.7078.1
http://dx.doi.org/10.1038/npre.2012.7078.1
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| Fonte: |
Nature Precedings
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| Direitos: |
Creative Commons Attribution 3.0 License
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