Background Lamins are the major structural proteins inside the nuclear lamina and their alterations are implicated in relatively few diseases, classified as laminopathies. In addition, lamin alterations have been described as playing a role in some neurodegenerative diseases, such as adult onset autosomal dominant leukodistrophy and Parkinson’s disease. We have recently described increased lamin B levels in in the putamen of Huntington’s disease (HD) patients, as well as in the striatum of R6/1 mouse model of HD (Rue et al., 2014).
Aims To analyse lamin B protein isoforms levels, B1 and B2, and also lamins A and C in R6/1 mice at different stages of the disease.
Methods/techniques Striatum, cortex and hippocampus from mice brain and postmortem human brain samples have been analysed by western blot and immunohistochemistry.
Results/outcome We found that R6/1 mice displayed increased lamin B1 and B2 levels in the striatum and cortex from early stages of the disease while in the hippocampus their levels were only augmented at late stages. Lamin A and C levels were also enhanced in the striatum and hippocampus at late stages, but they were not altered in the cortex. In contrast, protein levels of the lamin B receptor were unaltered. Immunohistochemical analysis showed that lamin B1 was clearly redistributed inside the nucleus, which presented irregular forms in R6/1 mice brain regions when compared with wild-type mice.
Conclusions Due to the role of lamin in chromatin organisation, gene transcription and oxidative stress responses, our results suggest that these alterations could have important implications in the pathophysiology of HD. Thus, normalising lamin protein levels could be a potential therapeutic strategy in the fight against this devastating neurodegenerative disease.
This work was supported by Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, (grant numbers PI13/01250 to EP-N and RETICS: RD06/0010/0006) and Ministerio de Ciencia e innovación (SAF2011–29507 to JA). R.A. is a fellow of Ministerio de Economia y Competitividad, Spain.
- Lamin B1
- Nuclear morphology
- R6/1 mice