Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease leading to muscular atrophy. 5–10% of total ALS cases are familial, the 20% of them having a mutation in the SOD1 gene, but most cases are sporadic; moreover the onset could be both spinal and bulbar. Retraction of motor axons from the synaptic connections with muscle is one of the earliest presymptomatic events. Understanding the role of muscle in ALS could have implications for the disease treatment, since, despite the broader etiology of human ALS, muscle impairment represents the common endpoint of the disease, indicating that results provided by studies conducted on animal models could be translated to patients. A proteomic and signalling study performed in a transgenic SOD1G93A mouse model showed that differential changes in muscle proteome can act as signalling events inducing progressive damage both at the muscular and motoneuronal levels [1]. The same differential proteomics approach was conducted in ALS patients. We examined the proteomic profiles of vastus lateralis muscles from 8 sporadic and a SOD1-mutated (L144F) patients by two-dimensional difference in gel electrophoresis (2-D DIGE) and mass spectrometry. Healthy age-matched subjects were considered as controls. According to the animal model proteomic study, variations were observed in mitochondrial structure, respiratory chain and TCA cycle, in anaerobic metabolism and in contractile/structural proteins. Signalling molecules were also monitored, providing a set of putative markers for validation in a larger patients’ cohort. Validation of these changes will represent an important step forward for diagnosis and monitoring of the disease progression in ALS patients.

Muscle molecular signature in sporadic ALS patients / L. Barbalini, D. Capitanio, M. Vasso, A. Ratti, V. Silani, C. Gelfi, D. Capitanio. ((Intervento presentato al 7. convegno ItPA Annual National Conference tenutosi a Viterbo nel 2012.

Muscle molecular signature in sporadic ALS patients

L. Barbalini
Primo
;
D. Capitanio
Secondo
;
A. Ratti;V. Silani
Penultimo
;
C. Gelfi
Ultimo
;
D. Capitanio
2012

Abstract

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease leading to muscular atrophy. 5–10% of total ALS cases are familial, the 20% of them having a mutation in the SOD1 gene, but most cases are sporadic; moreover the onset could be both spinal and bulbar. Retraction of motor axons from the synaptic connections with muscle is one of the earliest presymptomatic events. Understanding the role of muscle in ALS could have implications for the disease treatment, since, despite the broader etiology of human ALS, muscle impairment represents the common endpoint of the disease, indicating that results provided by studies conducted on animal models could be translated to patients. A proteomic and signalling study performed in a transgenic SOD1G93A mouse model showed that differential changes in muscle proteome can act as signalling events inducing progressive damage both at the muscular and motoneuronal levels [1]. The same differential proteomics approach was conducted in ALS patients. We examined the proteomic profiles of vastus lateralis muscles from 8 sporadic and a SOD1-mutated (L144F) patients by two-dimensional difference in gel electrophoresis (2-D DIGE) and mass spectrometry. Healthy age-matched subjects were considered as controls. According to the animal model proteomic study, variations were observed in mitochondrial structure, respiratory chain and TCA cycle, in anaerobic metabolism and in contractile/structural proteins. Signalling molecules were also monitored, providing a set of putative markers for validation in a larger patients’ cohort. Validation of these changes will represent an important step forward for diagnosis and monitoring of the disease progression in ALS patients.
Settore BIO/12 - Biochimica Clinica e Biologia Molecolare Clinica
Muscle molecular signature in sporadic ALS patients / L. Barbalini, D. Capitanio, M. Vasso, A. Ratti, V. Silani, C. Gelfi, D. Capitanio. ((Intervento presentato al 7. convegno ItPA Annual National Conference tenutosi a Viterbo nel 2012.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/255837
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