Changes in Collagen Metabolism in Diseased Muscle

Systematic Review and Meta-Analyses of Aminopeptidases as Prognostic Biomarkers in Amyotrophic Lateral Sclerosis

“…In diseases with spinal muscular atrophies, including ALS as a neurogenic muscle disease, they have elevated activities of lysosomal proteases and enzymes that accelerate the biosynthesis of muscle collagen [ 20 , 58 ]. Changes in population numbers of inflammatory fibroblasts and phagocytes occur together with increases in enzyme activities, which are accompanied by a proportionally similar increase in muscle collagen content in ALS [ 20 , 59 ]. The collagenase activities of the DPP1 and DPP4 enzymes present a positive correlation with several of the enzymatic activities related to collagen biosynthesis [ 20 ].…”

“…Furthermore, these increases in activities are usually positively correlated with the severity of muscle atrophy (rather than with specificity), where most acid hydrolytic and alkaline proteolytic activities are markedly increased only in severely diseased muscles [ 60 ]. Despite indicating rapid changes in post-translational modification of muscle collagen in ALS, the amount of collagen accumulated is not always perceived to be always consistent [ 61 ], nor are the changes in hydrolytic activities that reflect collagen biosynthesis and processing considered significant in other types of neuropathies with deposition of different types of collagens in the endomysium [ 59 , 61 ]. Other factors that cause variations in the activities are the age of the patient and the evolution of the diseases [ 61 ].…”

Systematic Review and Meta-Analyses of Aminopeptidases as Prognostic Biomarkers in Amyotrophic Lateral Sclerosis

“…In diseases with spinal muscular atrophies, including ALS as a neurogenic muscle disease, they have elevated activities of lysosomal proteases and enzymes that accelerate the biosynthesis of muscle collagen [ 20 , 58 ]. Changes in population numbers of inflammatory fibroblasts and phagocytes occur together with increases in enzyme activities, which are accompanied by a proportionally similar increase in muscle collagen content in ALS [ 20 , 59 ]. The collagenase activities of the DPP1 and DPP4 enzymes present a positive correlation with several of the enzymatic activities related to collagen biosynthesis [ 20 ].…”

“…Furthermore, these increases in activities are usually positively correlated with the severity of muscle atrophy (rather than with specificity), where most acid hydrolytic and alkaline proteolytic activities are markedly increased only in severely diseased muscles [ 60 ]. Despite indicating rapid changes in post-translational modification of muscle collagen in ALS, the amount of collagen accumulated is not always perceived to be always consistent [ 61 ], nor are the changes in hydrolytic activities that reflect collagen biosynthesis and processing considered significant in other types of neuropathies with deposition of different types of collagens in the endomysium [ 59 , 61 ]. Other factors that cause variations in the activities are the age of the patient and the evolution of the diseases [ 61 ].…”

Metabolomics Analysis of Skeletal Muscles from FKRP-Deficient Mice Indicates Improvement After Gene Replacement Therapy

“…We also observed alterations in some collagen-associated metabolites that could be associated with disease progression and/or accelerated aging. Collagen biosynthesis typically involves an unusually large number of enzyme-catalyzed post-translational modifications, many of which are unique to collagen and a few other proteins with collagen-like amino acid sequences 39,40 . These reactions include the hydroxylation of specific prolyl residues (e.g., trans-4-hydroxyproline) and glycosylation of hydroxylysine residues (e.g., 5-(galactosylhydroxy)-L-lysine).…”

Increased type III procollagen in serum and skin of patients with amyotrophic lateral sclerosis

“…Elevated serum PIIIP concentrations have been found in various liver diseases, such as alcoholic liver disease, acute and chronic hepatitis and primary biliary cirrhosis (24,25), myelofibrosis (26), cryptogenic fibrosing alveolitis (27), chronic endomyocardial fibrosis (28), polymyositis and muscular dystrophy (29), Paget's disease of bone (30), and malignant non-liver neoplasms (31). Several of these studies have demonstrated a strong correlation between serum propeptide levels and various parameters of collagen metabolism (26,29,31), showing that serum PIIIP may reflect the rate of type I11 collagen synthesis. Since neither ALS patients, diseased control subjects, nor healthy control ones in this study had the above disorders, a metabolic alteration of PIIIP may take place in the skin of ALS.…”

Systematic Review and Meta-Analyses of Aminopeptidases as Prognostic Biomarkers in Amyotrophic Lateral Sclerosis

“…In diseases with spinal muscular atrophies, including ALS as a neurogenic muscle disease, they have elevated activities of lysosomal proteases and enzymes that accelerate the biosynthesis of muscle collagen [ 20 , 58 ]. Changes in population numbers of inflammatory fibroblasts and phagocytes occur together with increases in enzyme activities, which are accompanied by a proportionally similar increase in muscle collagen content in ALS [ 20 , 59 ]. The collagenase activities of the DPP1 and DPP4 enzymes present a positive correlation with several of the enzymatic activities related to collagen biosynthesis [ 20 ].…”

“…Furthermore, these increases in activities are usually positively correlated with the severity of muscle atrophy (rather than with specificity), where most acid hydrolytic and alkaline proteolytic activities are markedly increased only in severely diseased muscles [ 60 ]. Despite indicating rapid changes in post-translational modification of muscle collagen in ALS, the amount of collagen accumulated is not always perceived to be always consistent [ 61 ], nor are the changes in hydrolytic activities that reflect collagen biosynthesis and processing considered significant in other types of neuropathies with deposition of different types of collagens in the endomysium [ 59 , 61 ]. Other factors that cause variations in the activities are the age of the patient and the evolution of the diseases [ 61 ].…”

Metabolomics Analysis of Skeletal Muscles from FKRP-Deficient Mice Indicates Improvement After Gene Replacement Therapy

“…We also observed alterations in some collagen-associated metabolites that could be associated with disease progression and/or accelerated aging. Collagen biosynthesis typically involves an unusually large number of enzyme-catalyzed post-translational modifications, many of which are unique to collagen and a few other proteins with collagen-like amino acid sequences 39,40 . These reactions include the hydroxylation of specific prolyl residues (e.g., trans-4-hydroxyproline) and glycosylation of hydroxylysine residues (e.g., 5-(galactosylhydroxy)-L-lysine).…”

Increased type III procollagen in serum and skin of patients with amyotrophic lateral sclerosis

“…Elevated serum PIIIP concentrations have been found in various liver diseases, such as alcoholic liver disease, acute and chronic hepatitis and primary biliary cirrhosis (24,25), myelofibrosis (26), cryptogenic fibrosing alveolitis (27), chronic endomyocardial fibrosis (28), polymyositis and muscular dystrophy (29), Paget's disease of bone (30), and malignant non-liver neoplasms (31). Several of these studies have demonstrated a strong correlation between serum propeptide levels and various parameters of collagen metabolism (26,29,31), showing that serum PIIIP may reflect the rate of type I11 collagen synthesis. Since neither ALS patients, diseased control subjects, nor healthy control ones in this study had the above disorders, a metabolic alteration of PIIIP may take place in the skin of ALS.…”

Systematic Review and Meta-Analyses of Aminopeptidases as Prognostic Biomarkers in Amyotrophic Lateral Sclerosis

“…In diseases with spinal muscular atrophies, including ALS as a neurogenic muscle disease, they have elevated activities of lysosomal proteases and enzymes that accelerate the biosynthesis of muscle collagen [ 20 , 58 ]. Changes in population numbers of inflammatory fibroblasts and phagocytes occur together with increases in enzyme activities, which are accompanied by a proportionally similar increase in muscle collagen content in ALS [ 20 , 59 ]. The collagenase activities of the DPP1 and DPP4 enzymes present a positive correlation with several of the enzymatic activities related to collagen biosynthesis [ 20 ].…”

“…Furthermore, these increases in activities are usually positively correlated with the severity of muscle atrophy (rather than with specificity), where most acid hydrolytic and alkaline proteolytic activities are markedly increased only in severely diseased muscles [ 60 ]. Despite indicating rapid changes in post-translational modification of muscle collagen in ALS, the amount of collagen accumulated is not always perceived to be always consistent [ 61 ], nor are the changes in hydrolytic activities that reflect collagen biosynthesis and processing considered significant in other types of neuropathies with deposition of different types of collagens in the endomysium [ 59 , 61 ]. Other factors that cause variations in the activities are the age of the patient and the evolution of the diseases [ 61 ].…”

Metabolomics Analysis of Skeletal Muscles from FKRP-Deficient Mice Indicates Improvement After Gene Replacement Therapy

“…We also observed alterations in some collagen-associated metabolites that could be associated with disease progression and/or accelerated aging. Collagen biosynthesis typically involves an unusually large number of enzyme-catalyzed post-translational modifications, many of which are unique to collagen and a few other proteins with collagen-like amino acid sequences 39,40 . These reactions include the hydroxylation of specific prolyl residues (e.g., trans-4-hydroxyproline) and glycosylation of hydroxylysine residues (e.g., 5-(galactosylhydroxy)-L-lysine).…”

Increased type III procollagen in serum and skin of patients with amyotrophic lateral sclerosis

“…Elevated serum PIIIP concentrations have been found in various liver diseases, such as alcoholic liver disease, acute and chronic hepatitis and primary biliary cirrhosis (24,25), myelofibrosis (26), cryptogenic fibrosing alveolitis (27), chronic endomyocardial fibrosis (28), polymyositis and muscular dystrophy (29), Paget's disease of bone (30), and malignant non-liver neoplasms (31). Several of these studies have demonstrated a strong correlation between serum propeptide levels and various parameters of collagen metabolism (26,29,31), showing that serum PIIIP may reflect the rate of type I11 collagen synthesis. Since neither ALS patients, diseased control subjects, nor healthy control ones in this study had the above disorders, a metabolic alteration of PIIIP may take place in the skin of ALS.…”