Activation of matrix metalloproteinase‐3 is altered at the frog neuromuscular junction following changes in synaptic activity

VanSaun, Michael N.; Humburg, B.C.; Arnett, Melinda G.; Pence, Matthew G.; Werle, M. J.

doi:10.1002/dneu.20523

Cited by 24 publications

(19 citation statements)

References 31 publications

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“…Interestingly, MMP‐3 is expressed by PSCs at the NMJ and its expression is tightly regulated according to innervation state (VanSaun et al . ). Moreover, persistence of agrin due to genetic deletion of MMP‐3 leads to the preservation of endplates following nerve injury and degeneration (Chao et al .…”

Section: Als‐related Electrophysiological Changes In Mns and Nmjsmentioning

confidence: 97%

“…Second, since agrin levels are controlled in part through degradation by matrix metalloproteinases (MMPs) (Darabid et al 2014), PSCs may regulate agrin levels by changing their secretion of MMPs. Interestingly, MMP-3 is expressed by PSCs at the NMJ and its expression is tightly regulated according to innervation state (VanSaun et al 2007). Moreover, persistence of agrin due to genetic deletion of MMP-3 leads to the preservation of endplates following nerve injury and degeneration (Chao et al 2012) and modulation of neuronal MMP-9 levels significantly delays muscle denervation (Kaplan et al 2014).…”

Section: Molecular and Age-dependent Interactions At The Nmj In Alsmentioning

confidence: 99%

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New perspectives on amyotrophic lateral sclerosis: the role of glial cells at the neuromuscular junction

Arbour

Velde

Robitaille

2016

The Journal of Physiology

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Amyotrophic lateral sclerosis (ALS) is a disease leading to the death of motor neurons (MNs). It is also recognized as a non-cell autonomous disease where glial cells in the CNS are involved in its pathogenesis and progression. However, although denervation of neuromuscular junctions (NMJs) represents an early and major event in ALS, the importance of glial cells at this synapse receives little attention. An interesting possibility is that altered relationships between glial cells and MNs in the spinal cord in ALS may also take place at the NMJ. Perisynaptic Schwann cells (PSCs), which are glial cells at the NMJ, show great morphological and functional adaptability to ensure NMJ stability, maintenance and repair. More specifically, PSCs change their properties according to the state of innervation. Hence, abnormal changes or lack of changes can have detrimental effects on NMJs in ALS. This review will provide an overview of known and hypothesized interactions between MN nerve terminals and PSCs at NMJs during development, aging and ALS-induced denervation. These neuron-PSC interactions may be crucial to the understanding of how degenerative changes begin and progress at NMJs in ALS, and represent a novel therapeutic target.

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Section: Als‐related Electrophysiological Changes In Mns and Nmjsmentioning

confidence: 97%

Section: Molecular and Age-dependent Interactions At The Nmj In Alsmentioning

confidence: 99%

New perspectives on amyotrophic lateral sclerosis: the role of glial cells at the neuromuscular junction

Arbour

Velde

Robitaille

2016

The Journal of Physiology

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“…A previous study has shown that serum levels of MMP3 are increased in GMG patients [9]. Our subgroup of 19 patients may have an increased risk of developing a more generalized and severe MG. MMP3 degrades agrin [34], and reduced synaptic activity downregulates its activity [22]. MMP-induced changes in agrin concentration and function can therefore lead to disturbances in agrin-mediated maintenance of the neuromuscular junction.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have suggested MMP9 to be an important factor in multiple sclerosis (MS) [18]. MMP2 and MMP3 activate MMP9 [19,20,21], and MMP2 and MMP9 are potent activators of MMP3 [22]. …”

Section: Introductionmentioning

confidence: 99%

Matrix Metalloproteinases in Myasthenia Gravis

Helgeland

Petzold²,

Luckman³

et al. 2011

Eur Neurol

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Introduction: Myasthenia gravis (MG) is an autoimmune disease with weakness in striated musculature due to anti-acetylcholine receptor (AChR) antibodies or muscle specific kinase at the neuromuscular junction. A subgroup of patients has periocular symptoms only; ocular MG (OMG). Matrix metalloproteinases (MMP) are increased in several autoimmune diseases, including generalized MG (GMG), and have been suggested to play a role in immune cell infiltration, basement membrane breakdown and autoimmune pathogenesis. Methods: Total levels of MMP2, MMP3 and MMP9 were measured in serum by ELISA. Results: The MG patients had increased serum levels of MMP2 (median values 200.7 vs. 159.7 ng/ml, p < 0.001) and MMP9 (median values 629.6 vs. 386.4 ng/ml, p < 0.001) compared to controls. A subgroup of patients had increased MMP3 concentration (p = 0.001). The differences were not dependent on presence of AChR antibodies. No difference was observed between GMG and OMG patients with regard to MMP2 (p = 0.598), MMP3 (p = 0.450) and MMP9 (p = 0.271). Discussion: The increased MMP levels in our MG patients group and the lack of dependence on anti-AChR antibodies suggest that MMP2, MMP3 and MMP9 play a role in the development of MG. The similarities between GMG and OMG support OMG as a systemic disease.

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“…However, one could hypothesize about their role in regulating agrin levels through MMP-MMP interaction. We know that MMP-2 and MMP-3 are able to activate MMP-9 [54,55,56,57], whereas MMP-2 and MMP-9 are potent activators of MMP-3 [58]. Agrin is a substrate for MMP-3 [59].…”

Section: Serum Levels Of Mmps In Mgmentioning

confidence: 99%

Serum Levels of Matrix Metalloproteinases: Implications in Clinical Neurology

Romi

Helgeland²,

Gilhus³

2012

Eur Neurol

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Matrix metalloproteinases (MMPs) are zinc-dependent enzymes involved in remodeling extracellular matrix and cell-matrix interactions. A pathogenic role of MMPs in neurological disorders is likely. This paper focuses on serological clinical aspects only. In multiple sclerosis, higher serum MMP-3 is seen during relapses. Lower serum MMP-8 and -9 levels correlate with fewer contrast-enhanced T₂-weighted MRI lesions, and serum MMP-9 can be used in monitoring treatment. In myasthenia gravis, serum MMP-2, -3, and -9 levels are elevated in both generalized and ocular diseases. A proportion of the patients have markedly increased serum MMP-3. In acute stroke, higher serum MMP-9 correlates with larger infarct volume, stroke severity, and worse functional outcome, and serum MMP-3 is significantly lower than in several other neurological disorders and healthy controls. In amyotrophic lateral sclerosis, serum MMP-2 correlates with disease progression, and both serum MMP-1 and -2 are elevated. In Alzheimer’s disease, serum MMP-3, -9, and -10 are elevated. In migraine, serum MMP-2 is elevated, and also MMP-9 in those patients with migraine without aura. MMP-9 is implicated in the pathogenesis of experimental epilepsy. A pathogenic role of MMPs in these conditions could be related to their ability to degrade extracellular matrix. MMPs may also facilitate autoimmunity.

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Activation of matrix metalloproteinase‐3 is altered at the frog neuromuscular junction following changes in synaptic activity

Cited by 24 publications

References 31 publications

New perspectives on amyotrophic lateral sclerosis: the role of glial cells at the neuromuscular junction

New perspectives on amyotrophic lateral sclerosis: the role of glial cells at the neuromuscular junction

Matrix Metalloproteinases in Myasthenia Gravis

Serum Levels of Matrix Metalloproteinases: Implications in Clinical Neurology

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