Is the expression of [-G93A(+)] human SOD1 a model to study neurodegenerations?

To relate the alterations occurring in neurodegenerations with Ca2+ homeostasis dysregulation, we analyzed the functional properties of the Ca2+-dependent calpaini calpastatin system in neuronal cells of transgenic mice overexpressing human mutated -G93A(+) SOD1. Motor cortex and spinal cord lower segments from transgenic mice show a very large increase in free Ca2+ ions and evident calpain activation, identified on the basis of its consumption and substrates digestion. Changes in calpastatin intracellular localization and calpain conformation state further support these observations. Moreover, calpastatin is significantlye expressed, counteracting its calpain-mediated degradation. Thus, the calpainIcalpastatin system may be a target for new therapeutic approaches to neurodegenerative diseases.