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

Abstract

To relate the alterations occurring in neurodegenerations with Ca²⁺ homeostasis dysregulation, we analyzed the functional properties of the Ca²⁺-dependent calpain/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 onthe basis of its consumption and substrates digestion. Changes in calpastatin intracellular localization and calpain conformation state further support these observations. Moreover, calpastatin is significantly expressed, counteracting its calpain-mediated degradation. Thus, the calpain /calpastatin system may be a target for new therapeutic approaches to neurodegenerative diseases.

Keywords

• Ca2 -dependent proteolysis
• calpain
• calpastatin
• NOS
• ALS