title: Calpain activation and CaMKIV reduction in spinal cords from hSOD1G93A mouse model.
abstract: 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 associated with 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 from spinal 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 pathogenesis.
authors: Unitat de Senyalització Neuronal, Dept Ciencies Mediques Basiques, Facultat de Medicina, Universitat de Lleida, IRBLLEIDA, Rovira Roure, 80, 25198 Lleida, Spain.
authors: Myriam
authors: M
authors: Gou-Fabregas
authors: Dept Medicina Experimental, Facultat de Medicina, Universitat de Lleida, IRBLLEIDA, Rovira Roure, 80, 25198 Lleida, Spain.
authors: Omar
authors: O
authors: Ramírez-Núñez
authors: Dept Medicina Experimental, Facultat de Medicina, Universitat de Lleida, IRBLLEIDA, Rovira Roure, 80, 25198 Lleida, Spain.
authors: Daniel
authors: D
authors: Cacabelos
authors: Unitat de Senyalització Neuronal, Dept Ciencies Mediques Basiques, Facultat de Medicina, Universitat de Lleida, IRBLLEIDA, Rovira Roure, 80, 25198 Lleida, Spain.
authors: Nuria
authors: N
authors: Bahi
authors: Dept Medicina Experimental, Facultat de Medicina, Universitat de Lleida, IRBLLEIDA, Rovira Roure, 80, 25198 Lleida, Spain.
authors: Manuel
authors: M
authors: Portero
authors: Unitat de Senyalització Neuronal, Dept Ciencies Mediques Basiques, Facultat de Medicina, Universitat de Lleida, IRBLLEIDA, Rovira Roure, 80, 25198 Lleida, Spain.
authors: Ana
authors: A
authors: Garcera
authors: Unitat de Senyalització Neuronal, Dept Ciencies Mediques Basiques, Facultat de Medicina, Universitat de Lleida, IRBLLEIDA, Rovira Roure, 80, 25198 Lleida, Spain. Electronic address: rosa.soler@cmb.udl.cat.
authors: Rosa M
authors: RM
authors: Soler
mesh_terms: D000367:Age Factors; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000473:pathology*; D000704:Analysis of Variance; D000818:Animals; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4 / Q000378:metabolism*; D002154:Calpain / Q000378:metabolism*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004622:Embryo, Mammalian; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D013482:Superoxide Dismutase / Q000235:genetics
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4; C517685:Camk4 protein, mouse; D002154:Calpain; D011188:Potassium
keywords: ALS; CaMKIV; Calpain; Intracellular calcium; Neurodegeneration; hSOD1G93A