PT  - JOURNAL ARTICLE
AU  - Faber, Peter W.
AU  - Alter, Janet R.
AU  - MacDonald, Marcy E.
AU  - Hart, Anne C.
TI  - Polyglutamine-mediated dysfunction and apoptotic death of a <em>Caenorhabditis elegans</em> sensory neuron
AID  - 10.1073/pnas.96.1.179
DP  - 1999 Jan 05
TA  - Proceedings of the National Academy of Sciences
PG  - 179--184
VI  - 96
IP  - 1
4099  - http://www.pnas.org/content/96/1/179.short
4100  - http://www.pnas.org/content/96/1/179.full
SO  - Proc Natl Acad Sci USA1999 Jan 05; 96
AB  - The effect of expressing human huntingtin fragments containing polyglutamine (polyQ) tracts of varying lengths was assessed in Caenorhabditis elegans ASH sensory neurons in young and old animals. Expression of a huntingtin fragment containing a polyQ tract of 150 residues (Htn-Q150) led to progressive ASH neurodegeneration but did not cause cell death. Progressive cell death and enhanced neurodegeneration were observed in ASH neurons that coexpressed Htn-Q150 and a subthreshold dose of a toxic OSM-10∷green fluorescent protein (OSM-10∷GFP) fusion protein. Htn-Q150 huntingtin protein fragments formed protein aggregates in ASH neurons, and the number of ASH neurons containing aggregates increased as animals aged. ASH neuronal cell death required ced-3 caspase function, indicating that the observed cell death is apoptotic. Of interest, ced-3 played a critical role in Htn-Q150-mediated neurodegeneration but not in OSM10∷GFP-mediated ASH neurodegeneration. ced-3 function was important but not essential for the formation of protein aggregates. Finally, behavioral assays indicated that ASH neurons, coexpressing Htn-Q150 and OSM10∷GFP, were functionally impaired at 3 days before the detection of neurodegeneration, cell death, and protein aggregates. HD,Huntington’s disease;GFP,green fluorescent protein;DiD,1,1′-dioctadecyl-3,3,3′,3′-tetramethylindodicarbocynanine perchlorate