2 research outputs found
Calpain activation and CaMKIV reduction in spinal cords from hSOD1G93A mouse model
Amyotrophic Lateral Sclerosis (ALS), a severe neurodegenerative disease, affects the upper and lower motor neurons
in the brain and spinal cord. In some studies, ALS disease progression has been associatedwith an increase in
calcium-dependent degeneration processes.Motoneurons are specifically vulnerable to sustained membrane depolarization
and excessive elevation of intracellular calcium concentration. The present study analyzed intracellular
events in embryonic motoneurons and adult spinal cords of the hSOD1G93A ALS mouse model. We
observed activation of calpain, a calcium-dependent cysteine protease that degrades a variety of substrates,
and a reduction in calcium–calmodulin dependent protein kinase type IV (CaMKIV) levels in protein extracts
fromspinal cords obtained at several time-points of hSOD1G93A mice disease progression. However, in cultured
embryonic motoneurons these differences between controls and hSOD1G93A mutants are not evident. Our results
support the hypothesis that age-dependent changes in calcium homeostasis and resulting events,
e.g., calpain activation and CaMKIV processing, are involved in ALS pathogenesi