| First Author | Anglada-Huguet M | Year | 2012 |
| Journal | J Neurochem | Volume | 121 |
| Issue | 4 | Pages | 639-48 |
| PubMed ID | 22372926 | Mgi Jnum | J:184365 |
| Mgi Id | MGI:5320810 | Doi | 10.1111/j.1471-4159.2012.07711.x |
| Citation | Anglada-Huguet M, et al. (2012) Activation of Elk-1 participates as a neuroprotective compensatory mechanism in models of Huntington's disease. J Neurochem 121(4):639-48 |
| abstractText | The transcription factor Elk-1 has been revealed as neuroprotective against toxic stimuli. In this study, we explored the neuroprotective capacity of Elk-1 in Huntington's disease. To this aim, we used two exon-1 mutant huntingtin (mhtt) mouse models (R6/1 and R6/2), and a full-length mhtt striatal cell model (STHdh(Q111/Q111) ). Analysis of Elk-1 and pElk-1(Ser383) in the striatum of R6 mice revealed increased levels during the disease progression. Similarly, Elk-1 and pElk-1(Ser383) levels were increased in STHdh(Q111/Q111) cells when compared with wild-type cells. In addition, we observed a predominant nuclear localization of Elk-1 in STHdh(Q111/Q111) cells, and in the striatum of 30-week-old R6/1 mice. Nuclear Elk-1 did not colocalize with mhtt aggregates, suggesting a higher transcriptional activity. In agreement, the knock-down of Elk-1 decreased immediate early genes expression in STHdh(Q111/Q111) cells, but not in wild-type cells. Interestingly, reduction of Elk-1 levels by siRNAs transfection promoted cell death and caspase 3 cleavage in STHdh(Q111/Q111) cells, but not in wild-type cells. In summary, we propose that increased protein levels, phosphorylation and nuclear localization of Elk-1 observed in exon-1 and full-length Huntington's disease models could be a compensatory mechanism activated by striatal cells in response to the presence of mhtt that contributes to neuroprotection. |
