Understanding the molecular consequences of inherited muscular dystrophies: advancements through proteomic experimentation

ABSTRACT Introduction: Proteomic techniques offer insights into the molecular perturbations occurring in muscular-dystrophies (MD). Revisiting published datasets can highlight conserved downstream molecular alterations, which may be worth re-assessing to determine whether their experimental manipulation is capable of modulating disease severity. Areas covered: Here, we review the MD literature, highlighting conserved molecular insights warranting mechanistic investigation for therapeutic potential. We also describe a workflow currently proving effective for efficient identification of biomarkers & therapeutic targets in other neurodegenerative conditions, upon which future MD proteomic investigations could be modelled. Expert commentary: Studying disease models can be useful for identifying biomarkers and model specific degenerative cascades, but rarely offer translatable mechanistic insights into disease pathology. Conversely, direct analysis of human samples undergoing degeneration presents challenges derived from complex chronic degenerative molecular processes. This requires a carefully planed & reproducible experimental paradigm accounting for patient selection through to grouping by disease severity and ending with proteomic data filtering and processing.

• Publication year

  2016

• Venue

  Espert Review of Proteomics

• Publication date

  2016-07-02

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1080/14789450.2016.1202768PMID 27329572
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• A systematic review of risk factors associated with muscular dystrophies

  2017cited by this paper
• Where do we stand in trial readiness for autosomal recessive limb girdle muscular dystrophies?

  2016cited by this paper
• Proteomic analysis of dystrophin deficiency and associated changes in the aged mdx-4cv heart model of dystrophinopathy-related cardiomyopathy.

  2016cited by this paper
• Redox Control of Antioxidant and Antihepatotoxic Activities of Cassia surattensis Seed Extract against Paracetamol Intoxication in Mice: In Vitro and In Vivo Studies of Herbal Green Antioxidant

  2016cited by this paper
• Commonality amid diversity: Multi-study proteomic identification of conserved disease mechanisms in spinal muscular atrophy.

  2016cited by this paper
• Identification of novel, therapy-responsive protein biomarkers in a mouse model of Duchenne muscular dystrophy by aptamer-based serum proteomics

  2015cited by this paper
• Advances in Muscular Dystrophies.

  2015cited by this paper
• The International Journal of Biochemistry & Cell Biology

  2015cited by this paper
• Membrane Injury and Repair in the Muscular Dystrophies

  2015cited by this paper
• Multi-level omics analysis in a murine model of dystrophin loss and therapeutic restoration

  2015cited by this paper
• A Systematic Review and Meta-analysis on the Epidemiology of the Muscular Dystrophies

  2015influential reference
• Modifier genes and their effect on Duchenne muscular dystrophy.

  2015cited by this paper
• Oxidative Stress-Mediated Skeletal Muscle Degeneration: Molecules, Mechanisms, and Therapies

  2015cited by this paper
• Comparative Label-Free Mass Spectrometric Analysis of Mildly versus Severely Affected mdx Mouse Skeletal Muscles Identifies Annexin, Lamin, and Vimentin as Universal Dystrophic Markers

  2015cited by this paper
• The immune system in Duchenne muscular dystrophy: Friend or foe

  2015cited by this paper
• Duchenne Muscular Dystrophy: From Diagnosis to Therapy

  2015cited by this paper
• Label-free mass spectrometric analysis reveals complex changes in the brain proteome from the mdx-4cv mouse model of Duchenne muscular dystrophy

  2015cited by this paper
• Label‐free mass spectrometric analysis of the mdx‐4cv diaphragm identifies the matricellular protein periostin as a potential factor involved in dystrophinopathy‐related fibrosis

  2015cited by this paper
• Simultaneous Pathoproteomic Evaluation of the Dystrophin-Glycoprotein Complex and Secondary Changes in the mdx-4cv Mouse Model of Duchenne Muscular Dystrophy

  2015cited by this paper
• Comparative proteomic analysis of the contractile-protein-depleted fraction from normal versus dystrophic skeletal muscle.

  2014cited by this paper
• Proteomics profiling of urine reveals specific titin fragments as biomarkers of Duchenne muscular dystrophy.

  2014cited by this paper
• A novel mouse model of Warburg Micro syndrome reveals roles for RAB18 in eye development and organisation of the neuronal cytoskeleton

  2014cited by this paper
• Prevalence of Muscular Dystrophies: A Systematic Literature Review

  2014cited by this paper
• Muscle proteomics reveals novel insights into the pathophysiological mechanisms of collagen VI myopathies.

  2014cited by this paper
• A systematic review and meta-analysis on the epidemiology of Duchenne and Becker muscular dystrophy

  2014cited by this paper
• Discovery of serum protein biomarkers in the mdx mouse model and cross-species comparison to Duchenne muscular dystrophy patients.

  2014cited by this paper
• Dysregulation of calcium homeostasis in muscular dystrophies

  2014cited by this paper
• Fibronectin is a serum biomarker for Duchenne muscular dystrophy

  2014cited by this paper
• Facioscapulohumeral Muscular Dystrophy As a Model for Epigenetic Regulation and Disease

  2014influential reference
• Chaperoning heat shock proteins: Proteomic analysis and relevance for normal and dystrophin‐deficient muscle

  2014cited by this paper
• Label-free quantitative proteomic profiling identifies disruption of ubiquitin homeostasis as a key driver of Schwann cell defects in spinal muscular atrophy.

  2014cited by this paper
• Dysregulation of ubiquitin homeostasis and β-catenin signaling promote spinal muscular atrophy.

  2014influential reference
• Comparative proteomic profiling of soleus, extensor digitorum longus, flexor digitorum brevis and interosseus muscles from the mdx mouse model of Duchenne muscular dystrophy

  2013cited by this paper
• Nesprins: from the nuclear envelope and beyond

  2013cited by this paper
• Muscular dystrophy: new challenges and review of the current clinical trials

  2013cited by this paper
• Calpains, Cleaved Mini-DysferlinC72, and L-Type Channels Underpin Calcium-Dependent Muscle Membrane Repair

  2013cited by this paper
• Identification of Disease Specific Pathways Using in Vivo SILAC Proteomics in Dystrophin Deficient mdx Mouse*

  2013cited by this paper
• Dystrophin deficiency leads to disturbance of LAMP1-vesicle-associated protein secretion

  2013cited by this paper
• Proteomic profiling of cardiomyopathic tissue from the aged mdx model of Duchenne muscular dystrophy reveals a drastic decrease in laminin, nidogen and annexin

  2013cited by this paper
• Label-free proteomics identifies Calreticulin and GRP75/Mortalin as peripherally accessible protein biomarkers for spinal muscular atrophy

  2013influential reference
• Myotonic dystrophy CTG expansion affects synaptic vesicle proteins, neurotransmission and mouse behaviour.

  2013cited by this paper
• Application of Fluorescence Two-Dimensional Difference In-Gel Electrophoresis as a Proteomic Biomarker Discovery Tool in Muscular Dystrophy Research

  2013cited by this paper
• Total Protein Analysis as a Reliable Loading Control for Quantitative Fluorescent Western Blotting

  2013cited by this paper
• UvA-DARE ( Digital Academic Repository ) Collagen VI mutations in Bethlem myopathy

  2012cited by this paper
• Protein profiling reveals energy metabolism and cytoskeletal protein alterations in LMNA mutation carriers.

  2012influential reference
• FSHD Myotubes with Different Phenotypes Exhibit Distinct Proteomes

  2012influential reference
• Profiling of Age-Related Changes in the Tibialis Anterior Muscle Proteome of the mdx Mouse Model of Dystrophinopathy

  2012cited by this paper
• Proteomics reveals drastic increase of extracellular matrix proteins collagen and dermatopontin in the aged mdx diaphragm model of Duchenne muscular dystrophy

  2012cited by this paper
• Pharmacologically targeting the primary defect and downstream pathology in Duchenne muscular dystrophy.

  2012cited by this paper
• Oxidative Damage in Muscular Dystrophy Correlates with the Severity of the Pathology: Role of Glutathione Metabolism

  2012cited by this paper
• Importance and challenge of making an early diagnosis in LMNA-related muscular dystrophy

  2012cited by this paper
• Duchenne muscular dystrophy--what causes the increased membrane permeability in skeletal muscle?

  2011cited by this paper
• Proteomic assessment of the acute phase of dystrophin deficiency in mdx mice

  2011cited by this paper
• Quantitative proteomic analysis of dystrophic dog muscle.

  2011cited by this paper
• [Collagen VI-related muscle disorders].

  2011cited by this paper
• Molecular Pathogenesis of Genetic and Inherited Diseases Delayed Cardiomyopathy in Dystrophin Deficient mdx Mice Relies on Intrinsic Glutathione Resource

  2010cited by this paper
• Mass spectrometry analysis of complexes formed by myotonic dystrophy protein kinase (DMPK).

  2010cited by this paper
• Proteomic profiling of naturally protected extraocular muscles from the dystrophin-deficient mdx mouse.

  2010cited by this paper
• Proteomic profiling of antisense‐induced exon skipping reveals reversal of pathobiochemical abnormalities in dystrophic mdx diaphragm

  2009cited by this paper
• Proteomics identification of differentially expressed proteins in the muscle of dysferlin myopathy patients

  2009cited by this paper
• A combined metabolomic and proteomic investigation of the effects of a failure to express dystrophin in the mouse heart.

  2008cited by this paper
• CTG Trinucleotide Repeat “Big Jumps”: Large Expansions, Small Mice

  2007influential reference
• Myotonic dystrophy: emerging mechanisms for DM1 and DM2.

  2007cited by this paper
• Dynamic responses of the glutathione system to acute oxidative stress in dystrophic mouse (mdx) muscles.

  2006cited by this paper
• Proteome analysis of the dystrophin‐deficient MDX diaphragm reveals a drastic increase in the heat shock protein cvHSP

  2006cited by this paper
• Proteomic investigation of the molecular pathophysiology of dysferlinopathy

  2006cited by this paper
• Reduced expression of regucalcin in young and aged mdx diaphragm indicates abnormal cytosolic calcium handling in dystrophin-deficient muscle.

  2006cited by this paper
• Parallel protein and transcript profiles of FSHD patient muscles correlate to the D4Z4 arrangement and reveal a common impairment of slow to fast fibre differentiation and a general deregulation of MyoD‐dependent genes

  2006influential reference
• Increased levels of adenine nucleotide translocator 1 protein and response to oxidative stress are early events in facioscapulohumeral muscular dystrophy muscle

  2005influential reference
• Collagen VI related muscle disorders

  2005cited by this paper
• Differential expression of the skeletal muscle proteome in mdx mice at different ages

  2004cited by this paper
• Immunoblot analysis of sarcoplasmic calcium binding proteins in Duchenne muscular dystrophy

  2004cited by this paper
• Albumin targeting of damaged muscle fibres in the mdx mouse can be monitored by MRI.

  2004cited by this paper
• Desmin and Vimentin as markers of regeneration in muscle diseases

  2004cited by this paper
• Insulin receptor splicing alteration in myotonic dystrophy type 2.

  2004cited by this paper
• Relationship between utrophin and regenerating muscle fibers in duchenne muscular dystrophy.

  2003cited by this paper
• 108th ENMC International Workshop, 3rd Workshop of the MYO-CLUSTER project: EUROMEN, 7th International Emery-Dreifuss Muscular Dystrophy (EDMD) Workshop, 13-15 September 2002, Naarden, The Netherlands.

  2003cited by this paper
• Proteomic analysis of mdx skeletal muscle: Great reduction of adenylate kinase 1 expression and enzymatic activity

  2003cited by this paper
• Defective membrane repair in dysferlin-deficient muscular dystrophy

  2003cited by this paper
• Loss of calpain-3 autocatalytic activity in LGMD2A patients with normal protein expression.

  2003cited by this paper
• Bethlem myopathy (BETHLEM) and Ullrich scleroatonic muscular dystrophy: 100th ENMC international workshop, 23-24 November 2001, Naarden, The Netherlands.

  2002cited by this paper
• Mutations in COL6A3 cause severe and mild phenotypes of Ullrich congenital muscular dystrophy.

  2002cited by this paper
• Mutations in COL 6 A 3 Cause Severe and Mild Phenotypes of Ullrich Congenital Muscular Dystrophy

  2002cited by this paper
• Aberrant regulation of insulin receptor alternative splicing is associated with insulin resistance in myotonic dystrophy

  2001cited by this paper
• Ullrich scleroatonic muscular dystrophy is caused by recessive mutations in collagen type VI

  2001cited by this paper
• Identification of mutations in the gene encoding lamins A/C in autosomal dominant limb girdle muscular dystrophy with atrioventricular conduction disturbances (LGMD1B).

  2000cited by this paper
• Different mutations in the LMNA gene cause autosomal dominant and autosomal recessive Emery-Dreifuss muscular dystrophy.

  2000cited by this paper
• Transgenic mice carrying large human genomic sequences with expanded CTG repeat mimic closely the DM CTG repeat intergenerational and somatic instability.

  2000cited by this paper
• Bethlem myopathy: a slowly progressive congenital muscular dystrophy with contractures.

  1999cited by this paper
• Mutations in the gene encoding lamin A/C cause autosomal dominant Emery-Dreifuss muscular dystrophy

  1999cited by this paper
• Dysferlin, a novel skeletal muscle gene, is mutated in Miyoshi myopathy and limb girdle muscular dystrophy

  1998cited by this paper
• Elevated Levels of Albumin in Soleus and Diaphragm Muscles of mdx Mice

  1996cited by this paper
• Muscle Disorders in Childhood, 2nd Ed.

  1996cited by this paper
• Mutations in the proteolytic enzyme calpain 3 cause limb-girdle muscular dystrophy type 2A.

  1995cited by this paper
• Bethlem myopathy: early-onset benign autosomal dominant myopathy with contractures. Description of two new families.

  1994cited by this paper
• Identification of a novel X-linked gene responsible for Emery-Dreifuss muscular dystrophy

  1994cited by this paper
• Disruptions of muscle fiber plasma membranes. Role in exercise-induced damage.

  1992cited by this paper
• Vimentin and desmin in maturing skeletal muscle and developmental myopathies

  1992cited by this paper
• Population frequencies of inherited neuromuscular diseases--a world survey.

  1991cited by this paper
• A developmental change in the content of parvalbumin in normal and dystrophic mouse (mdx) muscle.

  1990cited by this paper

• Optimized efficient screening for Duchenne muscular dystrophy carriers using proto-oncogene tyrosine-protein kinase receptor Ret.

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  2025cites this paper
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  2022cites this paper
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  2022cites this paper
• Histopathology of Duchenne muscular dystrophy in correlation with changes in proteomic biomarkers.

  2021cites this paper
• Proteomic profiling of fatty acid binding proteins in muscular dystrophy

  2020cites this paper
• Muscle cell differentiation and development pathway defects in Emery-Dreifuss muscular dystrophy.

  2020cites this paper
• Blood-derived biomarkers correlate with clinical progression in Duchenne muscular dystrophy

  2020cites this paper
• Proteomic profiling of giant skeletal muscle proteins

  2019cites this paper
• Proteomic profiling of the mouse diaphragm and refined mass spectrometric analysis of the dystrophic phenotype

  2019cites this paper
• Emerging proteomic biomarkers of X-linked muscular dystrophy

  2019cites this paper
• Chemical crosslinking analysis of β-dystroglycan in dystrophin-deficient skeletal muscle

  2018cites this paper
• Elucidating regulators and biomarkers of synaptic stability during neurodegeneration

  2018cites this paper
• Proteome and transcriptome profiling of equine myofibrillar myopathy identifies diminished peroxiredoxin 6 and altered cysteine metabolic pathways

  2018cites this paper
• Proteomic analysis of the sarcolemma-enriched fraction from dystrophic mdx-4cv skeletal muscle.

  2018cites this paper
• Proteomic Profiling of the Dystrophin-Deficient Brain.

  2018cites this paper
• Loss of Dystrobrevin Causes Muscle Degeneration and a Short Lifespan in Caenorhabditis elegans

  2018cites this paper
• Proteomic profiling of the dystrophin complex and membrane fraction from dystrophic mdx muscle reveals decreases in the cytolinker desmoglein and increases in the extracellular matrix stabilizers biglycan and fibronectin

  2017cites this paper
• Mass spectrometric identification of dystrophin, the protein product of the Duchenne muscular dystrophy gene, in distinct muscle surface membranes

  2017cites this paper
• Proteomic profiling of mdx-4cv serum reveals highly elevated levels of the inflammation-induced plasma marker haptoglobin in muscular dystrophy

  2017cites this paper
• Protein biomarkers analysis within muscular dystrophies

  2017cites this paper
• Bridging the gap: large animal models in neurodegenerative research

  2017cites this paper
• Neues aus der neuromuskulären Grundlagenforschung

  2017cites this paper