Amyotrophic lateral sclerosis (ALS) is a fatal, neurodegenerative disorder characterized by the selective loss of motor neurons from the spinal cord and brain. About 10% of ALS cases are familial (FALS), and in 20% of these cases the disease has been linked to mutations in the Cu,Zn-SOD1 gene. Although the molecular mechanisms causing these forms of ALS are still unclear, evidence has been provided that motor neurons injuries associated with mutant superoxide dismutase (SOD1)-related FALS result from a toxic gain-in-fuction of the mutated enzyme. To understand better the role of these mutations in the pathophysiology of FALS we have compared the pattern of proteins expressed in human neuroblastoma SH-SY5Y cell line with those of cell lines transfected with plasmids expressing the wild-type human SOD1 and the H46R and G93A mutants. 2-DE coupled to MALDI-TOF-MS were the proteomic tools used for identification of differentially expressed proteins. These included cytoskeletal proteins, proteins that regulate energetic metabolism and intracellular redox conditions, and the ubiquitin proteasome system. The proteomic approach allowed to expand the knowledge on the pattern of proteins, with altered expression, which we should focus on, for a better understanding of the possible mechanism involved in mutated-SOD1 toxicity. The cellular models considered in this work have also evidenced biochemical characteristics common to other SOD1-mutated cellular lines connected to the pathogenesis of ALS.

Di Poto, C., Iadarola, P., Bardoni, A., Passadore, I., Giorgetti, S., Cereda, C., et al. (2007). 2-DE and MALDI-TOF-MS for a comparative analysis of proteins expressed in different cellular models of amyotrophic lateral sclerosis. ELECTROPHORESIS, 28(23), 4320-4329 [10.1002/elps.200700455].

2-DE and MALDI-TOF-MS for a comparative analysis of proteins expressed in different cellular models of amyotrophic lateral sclerosis

CARRI', MARIA TERESA;
2007

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal, neurodegenerative disorder characterized by the selective loss of motor neurons from the spinal cord and brain. About 10% of ALS cases are familial (FALS), and in 20% of these cases the disease has been linked to mutations in the Cu,Zn-SOD1 gene. Although the molecular mechanisms causing these forms of ALS are still unclear, evidence has been provided that motor neurons injuries associated with mutant superoxide dismutase (SOD1)-related FALS result from a toxic gain-in-fuction of the mutated enzyme. To understand better the role of these mutations in the pathophysiology of FALS we have compared the pattern of proteins expressed in human neuroblastoma SH-SY5Y cell line with those of cell lines transfected with plasmids expressing the wild-type human SOD1 and the H46R and G93A mutants. 2-DE coupled to MALDI-TOF-MS were the proteomic tools used for identification of differentially expressed proteins. These included cytoskeletal proteins, proteins that regulate energetic metabolism and intracellular redox conditions, and the ubiquitin proteasome system. The proteomic approach allowed to expand the knowledge on the pattern of proteins, with altered expression, which we should focus on, for a better understanding of the possible mechanism involved in mutated-SOD1 toxicity. The cellular models considered in this work have also evidenced biochemical characteristics common to other SOD1-mutated cellular lines connected to the pathogenesis of ALS.
Pubblicato
Rilevanza internazionale
Abstract
Sì, ma tipo non specificato
Settore BIO/10
English
Con Impact Factor ISI
Superoxide Dismutase; Cell Extracts; Spinal Cord; Apoptosis; Enzyme Activation; Humans; Models, Biological; Neuroblastoma; Oxidation-Reduction; Transfection; Amyotrophic Lateral Sclerosis; Cells, Cultured; Electrophoresis, Gel, Two-Dimensional; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Proteome; Cytosol; Proteins; Amino Acid Substitution; Cell Line; Neurofilament Proteins
Di Poto, C., Iadarola, P., Bardoni, A., Passadore, I., Giorgetti, S., Cereda, C., et al. (2007). 2-DE and MALDI-TOF-MS for a comparative analysis of proteins expressed in different cellular models of amyotrophic lateral sclerosis. ELECTROPHORESIS, 28(23), 4320-4329 [10.1002/elps.200700455].
Di Poto, C; Iadarola, P; Bardoni, A; Passadore, I; Giorgetti, S; Cereda, C; Carri', Mt; Ceroni, M; Salvini, R
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/34947
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