CUP Faculty Research
Title
Proximal Giant Neurofilamentous Axonopathy in Mice Genetically Engineered to Resist Calpain and Caspase Cleavage of α-II Spectrin
Document Type
Article
Publication Date
1-1-2012
Abstract
We use 1,2-diacetylbenzene (1,2-DAB) to probe molecular mechanisms of proximal giant neurofilamentous axonopathy (PGNA), a pathological hallmark of amyotrophic lateral sclerosis. The spinal cord proteome of rodents displaying 1,2-DAB-PGNA suggests a reduction in the abundance of αII-spectrin (Spna2), a key protein in the maintenance of axonal integrity. Protein immunoblotting indicates that this reduction is due Spna2 degradation. We investigated the importance of such degradation in 1,2-DAB-PGNA. Spna2 mutant mice lacking a calpain- and/or caspase-sensitive domain (CSD), thus hypothetically resistant to 1,2-DAB, and wild-type littermates, were treated with 1,2-DAB, 35 mg/kg/day, or saline-control, for 3 weeks. 1,2-DAB induced motor weakness and PGNA irrespective of the genotype. Spna2-calpain breakdown products were not detected in mutant mice, which displayed a normal structure of the nervous system under saline-treatment. Intriguingly, treatment with 1,2-DAB reduced the abundance of the caspase-specific 120 kDa Spna2 breakdown products. Our findings indicate that degradation of Spna2 by calpain- and/or caspase is not central to the pathogenesis of 1,2-DAB axonopathy. In addition, the Spna2-CSD seems to be not required for the maintenance of the cytoskeleton integrity. Our conceptual framework offers opportunities to study the role of calpain-caspase cross-talk, including that of the protease degradomics, in models of axonal degeneration.
Published In
Journal of Molecular Neuroscience
Recommended Citation
Kassa, R.; Monterroso, V.; Wentzell, J.; Ramos, A. L.; Couchi, E.; Lecomte, M. C.; Iordanov, M.; Kretzschmar, D.; Nicolas, G.; and Tshala-Katumbay, D., "Proximal Giant Neurofilamentous Axonopathy in Mice Genetically Engineered to Resist Calpain and Caspase Cleavage of α-II Spectrin" (2012). CUP Faculty Research. 124.
https://digitalcommons.csp.edu/cup_commons_faculty/124
Source
CU Commons -- Math and Science Department Faculty Research
Comments
Publication Information.
Kassa, R., Monterroso, V., Wentzell, J., Ramos, A. L., Couchi, E., Lecomte, M. C., Iordanov, M., Kretzschmar, D., Nicolas, G., & Tshala-Katumbay, D. (2012). Proximal giant neurofilamentous axonopathy in mice genetically engineered to resist calpain and caspase cleavage of α-II spectrin. Journal of Molecular Neuroscience, 47(3), 631-638. doi:10.1007/s12031-011-9699-8