Open AccessIs the expression of [-G93A(+)] human SOD1 a model to study neurodegenerations?
Author(s) -
Roberto Stifanese,
Monica Averna,
Marco Pedrazzi,
Roberta De Tullio,
Franca Salamino,
S. Pontremoli,
Edon Melloni
Publication year - 2011
Publication title -
journal of biological research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.218
H-Index - 6
eISSN - 2284-0230
pISSN - 1826-8838
DOI - 10.4081/jbr.2011.4501
Subject(s) - calpastatin , calpain , intracellular , genetically modified mouse , sod1 , microbiology and biotechnology , transgene , homeostasis , spinal cord , chemistry , biology , neuroscience , gene , biochemistry , mutant , enzyme
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