Glutamine/proline-rich PQE-1 proteins protect Caenorhabditis elegans neurons from huntingtin polyglutamine neurotoxicity
AUTOR(ES)
Faber, Peter W.
FONTE
National Academy of Sciences
RESUMO
Huntington's disease is a progressive neurodegenerative disease caused by a polyglutamine (polyQ) repeat expansion in the huntingtin protein [Huntington's Disease Collaborative Research Group (1993) Cell 72, 971–983]. To understand the mechanism by which polyQ repeats cause neurodegeneration and cell death, we modeled polyQ neurotoxicity in Caenorhabditis elegans. In our model, expression of N-terminal fragments of human huntingtin causes polyQ-dependent degeneration of neurons. We conducted a genetic screen to identify proteins that protect neurons from the toxic effects of expanded polyQ tracts. Loss of polyQenhancer-1 (pqe-1) gene function strongly and specifically exacerbates neurodegeneration and cell death, whereas overexpression of a pqe-1 cDNA protects C. elegans neurons from the toxic effects of expanded huntingtin fragments. A glutamine/proline-rich domain, along with a charged domain, is critical for PQE-1 protein function. Analysis of pqe-1 suggests that proteins exist that specifically protect neurons from the toxic effects of expanded polyQ disease proteins.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=139281Documentos Relacionados
- Polyglutamine aggregates alter protein folding homeostasis in Caenorhabditis elegans
- SUT-2 potentiates tau-induced neurotoxicity in Caenorhabditis elegans
- Polyglutamine-mediated dysfunction and apoptotic death of a Caenorhabditis elegans sensory neuron
- Mutations Affecting the Chemosensory Neurons of Caenorhabditis Elegans
- Neurotoxin-induced degeneration of dopamine neurons in Caenorhabditis elegans
