Cited by 30Muscle Physiology and DisordersAmyotrophic Lateral Sclerosis ResearchGenetic Neurodegenerative Diseases

Exercise Training Reverses Skeletal Muscle Atrophy in an Experimental Model of VCP Disease

Open access
Nalbandian, Angèle, Nguyen, Christopher, Katheria, Veeral, Llewellyn, Katrina J., Badadani, Mallikarjun, Caiozzo, Vincent, Kimonis, Virginia E.·2013·PLoS ONE

Abstract

BACKGROUND: The therapeutic effects of exercise resistance and endurance training in the alleviation of muscle hypertrophy/atrophy should be considered in the management of patients with advanced neuromuscular diseases. Patients with progressive neuromuscular diseases often experience muscle weakness, which negatively impact independence and quality of life levels. Mutations in the valosin containing protein (VCP) gene lead to Inclusion body myopathy associated with Paget's disease of bone and frontotemporal dementia (IBMPFD) and more recently affect 2% of amyotrophic lateral sclerosis (ALS)-diagnosed cases. METHODS/PRINCIPLE FINDINGS: The present investigation was undertaken to examine the effects of uphill and downhill exercise training on muscle histopathology and the autophagy cascade in an experimental VCP mouse model carrying the R155H mutation. Progressive uphill exercise in VCP(R155H/+) mice revealed significant improvement in muscle strength and performance by grip strength and Rotarod analyses when compared to the sedentary mice. In contrast, mice exercised to run downhill did not show any significant improvement. Histologically, the uphill exercised VCP(R155H/+) mice displayed an improvement in muscle atrophy, and decreased expression levels of ubiquitin, P62/SQSTM1, LC3I/II, and TDP-43 autophagy markers, suggesting an alleviation of disease-induced myopathy phenotypes. There was also an improvement in the Paget-like phenotype. CONCLUSIONS: Collectively, our data highlights that uphill exercise training in VCP(R155H/+) mice did not have any detrimental value to the function of muscle, and may offer effective therapeutic options for patients with VCP-associated diseases.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1371/journal.pone.0076187

Cites

45 of 45 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Muscle from IBMPFD patients carrying VCP mutations and transgenic mice expressing VCP mutants display accumulations of SQSTM1- and LC3-positive autophagosomes and abnormal mitochondria.

    “muscle from IBMPFD patients carrying VCP mutations [246] and transgenic mice expressing VCP mutants [244,248,249] display accumulations of SQSTM1- and LC3-positive autophagosomes and abnormal mitochondria [250,251].”

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

1 retracted

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Nalbandian, A., Nguyen, C., Katheria, V., Llewellyn, K. J., Badadani, M., Caiozzo, V., & Kimonis, V. E.
Affiliations
University of California, Irvine (US)
Corresponding author
Kimonis, Virginia E.
Venue
PLoS ONE
Published
2013-10-09
Volume
8
Issue
10
Pages
e76187
ISSN
1932-6203 (ISSN-L)
OpenAlex
W2012831734
Cited by
30
References
45
Citations by year
2025: 1 · 2024: 2 · 2023: 2 · 2022: 3 · 2021: 3 · 2020: 3 · 2019: 1 · 2018: 1 · 2017: 5 · 2016: 2 · 2015: 4 · 2014: 2
FWCI
1.20
Type
journal article
Language
en
Open access
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
Muscular Dystrophy Association (175682)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
Keywords
VCP, skeletal muscle atrophy, exercise training, uphill running, downhill running, autophagy, ubiquitin, p62, LC3, TDP-43, muscle strength, neuromuscular disorders, mouse model
MeSH terms
Valosin Containing Protein, Adenosine Triphosphatases, Animals, Autophagy, Disease Models, Animal, Mitochondria, Muscular Atrophy, Mutation, Phenotype, Physical Conditioning, Animal, Apoptosis, Muscle, Skeletal, Cell Cycle Proteins, Mice, Muscle Strength

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review