| First Author | Hogg MC | Year | 2016 |
| Journal | Biochim Biophys Acta | Volume | 1862 |
| Issue | 6 | Pages | 1063-73 |
| PubMed ID | 26976329 | Mgi Jnum | J:256007 |
| Mgi Id | MGI:6105480 | Doi | 10.1016/j.bbadis.2016.03.006 |
| Citation | Hogg MC, et al. (2016) Caspase 6 has a protective role in SOD1(G93A) transgenic mice. Biochim Biophys Acta 1862(6):1063-73 |
| abstractText | In amyotrophic lateral sclerosis (ALS), it has been suggested that the process of neurodegeneration starts at the neuromuscular junction and is propagated back along axons towards motor neurons. Caspase-dependent pathways are well established as a cause of motor neuron death, and recent work in other disease models indicated a role for caspase 6 in axonal degeneration. Therefore we hypothesised that caspase 6 may be involved in motor neuron death in ALS. To investigate the role of caspase 6 in ALS we profiled protein levels of caspase-6 throughout disease progression in the ALS mouse model SOD1(G93A); this did not reveal differences in caspase 6 levels during disease. To investigate the role of caspase 6 further we generated a colony with SOD1(G93A) transgenic mice lacking caspase 6. Analysis of the transgenic SOD1(G93A); Casp6(-/-) revealed an exacerbated phenotype with motor dysfunction occurring earlier and a significantly shortened lifespan when compared to transgenic SOD1(G93A); Casp6(+/+) mice. Immunofluorescence analysis of the neuromuscular junction revealed no obvious difference between caspase 6(+/+) and caspase 6(-/-) in non-transgenic mice, while the SOD1(G93A) transgenic mice showed severe degeneration compared to non-transgenic mice in both genotypes. Our data indicate that caspase-6 does not exacerbate ALS pathogenesis, but may have a protective role. |
