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Cited by 26Neuroscience and Neuropharmacology ResearchMuscle Physiology and DisordersNicotinic Acetylcholine Receptors Study

Skeletal muscle calpain acts through nitric oxide and neural miRNAs to regulate acetylcholine release in motor nerve terminals

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Zhu, Haipeng, Bhattacharyya, Bula J., Lin, Hong, Gomez, Christopher M.·2013·The Journal of Neuroscience
DOI 10.1523/jneurosci.0224-13.2013PMC PMC3753772
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Abstract

Cholinergic overactivity in diseases of neuromuscular transmission elicits a retrograde signal resembling homeostatic synaptic plasticity that downregulates transmitter release. Understanding this compensatory pathway could provide insights into novel therapeutic avenues and molecular mechanisms underlying learning and memory. Here we identify nitric oxide as a possible source of this signal in pathological human and mouse muscle samples and link this signaling pathway to changes in synaptic function in the neuromuscular junction. We further show that neuronal nitric oxide synthase is regulated by cholinergic excess through activation of skeletal muscle calpain and its effect on Cdk5 and CaMKII, leading to direct modulation of presynaptic function. Finally, we show that this signaling pathway acts through specific miRNA control of presynaptic vesicle protein expression. The control of presynaptic miRNA levels by postsynaptic activity represents a novel mechanism for the modulation of synaptic activity in normal or pathological conditions.

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  • miRNAs play an important role in neurodegenerative diseases, including ALS.

    “Growing evidence suggests that miRNAs play an important role in neurodegenerative diseases, including ALS (Akerblom et al., 2012; Goodall et al., 2013; Zhu et al., 2013; Parisi et al., 2016).”

    From Downregulation of MicroRNA-193b-3p Promotes Autophagy and Cell Survival by Targeting TSC1/mTOR Signaling in NSC-34 Cells (2017) · cites this paper as Zhu et al., 2013

    The Discussion (page unavailable) says there is growing recognition that miRNAs play a prominent role in neurological and muscular disease. The Results also demonstrate miRNA effects on motor-nerve-terminal function, but the passages found do not address ALS specifically. (LLM, conf=0.84)

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Cited by

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Authors
Zhu, H., Bhattacharyya, B. J., Lin, H., & Gomez, C. M.
Affiliations
  • University of Chicago Medical Center (US)
  • Northwestern University (US)
  • Children's Hospital of Philadelphia (US)
Corresponding author
Gomez, Christopher M.
ORCID
Venue
The Journal of Neuroscience
Publisher
Society for Neuroscience
Published
2013-04-24
Volume
33
Issue
17
Pages
7308-7324
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
DOI
10.1523/jneurosci.0224-13.2013
PMC
PMC3753772
OpenAlex
W1971988525
Cited by
26
References
2
Citations by year
2025: 1 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 1 · 2020: 3 · 2019: 2 · 2018: 3 · 2017: 4 · 2016: 1 · 2015: 1 · 2014: 4 · 2013: 2
FWCI
1.31
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
Funders
  • National Institutes of Health
  • National Institute of Neurological Disorders and Stroke (R01NS033202, #RO1 NS33202)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
Keywords
nitric oxide, neuronal nitric oxide synthase, acetylcholine release, neuromuscular junction, motor nerve terminals, cyclin-dependent kinase 5, CaMKII, microRNA, presynaptic modulation, neuromuscular transmission
MeSH terms
Acetylcholine, Animals, Calpain, Cell Line, Humans, Male, Motor Neurons, Nitric Oxide, Mice, Knockout, Muscle, Skeletal, MicroRNAs, Cell Line, Tumor, Mice, HEK293 Cells

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