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The Impact of Kinases in Amyotrophic Lateral Sclerosis at the Neuromuscular Synapse: Insights into BDNF/TrkB and PKC Signaling

Brain-derived neurotrophic factor (BDNF) promotes neuron survival in adulthood in the central nervous system. In the peripheral nervous system, BDNF is a contraction-inducible protein that, through its binding to tropomyosin-related kinase B receptor (TrkB), contributes to the retrograde neuroprotec...

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Autores principales: Lanuza, Maria A., Just-Borràs, Laia, Hurtado, Erica, Cilleros-Mañé, Víctor, Tomàs, Marta, Garcia, Neus, Tomàs, Josep
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6953086/
https://www.ncbi.nlm.nih.gov/pubmed/31817487
http://dx.doi.org/10.3390/cells8121578
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author Lanuza, Maria A.
Just-Borràs, Laia
Hurtado, Erica
Cilleros-Mañé, Víctor
Tomàs, Marta
Garcia, Neus
Tomàs, Josep
author_facet Lanuza, Maria A.
Just-Borràs, Laia
Hurtado, Erica
Cilleros-Mañé, Víctor
Tomàs, Marta
Garcia, Neus
Tomàs, Josep
author_sort Lanuza, Maria A.
collection PubMed
description Brain-derived neurotrophic factor (BDNF) promotes neuron survival in adulthood in the central nervous system. In the peripheral nervous system, BDNF is a contraction-inducible protein that, through its binding to tropomyosin-related kinase B receptor (TrkB), contributes to the retrograde neuroprotective control done by muscles, which is necessary for motor neuron function. BDNF/TrkB triggers downstream presynaptic pathways, involving protein kinase C, essential for synaptic function and maintenance. Undeniably, this reciprocally regulated system exemplifies the tight communication between nerve terminals and myocytes to promote synaptic function and reveals a new view about the complementary and essential role of pre and postsynaptic interplay in keeping the synapse healthy and strong. This signaling at the neuromuscular junction (NMJ) could establish new intervention targets across neuromuscular diseases characterized by deficits in presynaptic activity and muscle contractility and by the interruption of the connection between nervous and muscular tissues, such as amyotrophic lateral sclerosis (ALS). Indeed, exercise and other therapies that modulate kinases are effective at delaying ALS progression, preserving NMJs and maintaining motor function to increase the life quality of patients. Altogether, we review synaptic activity modulation of the BDNF/TrkB/PKC signaling to sustain NMJ function, its and other kinases’ disturbances in ALS and physical and molecular mechanisms to delay disease progression.
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spelling pubmed-69530862020-01-23 The Impact of Kinases in Amyotrophic Lateral Sclerosis at the Neuromuscular Synapse: Insights into BDNF/TrkB and PKC Signaling Lanuza, Maria A. Just-Borràs, Laia Hurtado, Erica Cilleros-Mañé, Víctor Tomàs, Marta Garcia, Neus Tomàs, Josep Cells Review Brain-derived neurotrophic factor (BDNF) promotes neuron survival in adulthood in the central nervous system. In the peripheral nervous system, BDNF is a contraction-inducible protein that, through its binding to tropomyosin-related kinase B receptor (TrkB), contributes to the retrograde neuroprotective control done by muscles, which is necessary for motor neuron function. BDNF/TrkB triggers downstream presynaptic pathways, involving protein kinase C, essential for synaptic function and maintenance. Undeniably, this reciprocally regulated system exemplifies the tight communication between nerve terminals and myocytes to promote synaptic function and reveals a new view about the complementary and essential role of pre and postsynaptic interplay in keeping the synapse healthy and strong. This signaling at the neuromuscular junction (NMJ) could establish new intervention targets across neuromuscular diseases characterized by deficits in presynaptic activity and muscle contractility and by the interruption of the connection between nervous and muscular tissues, such as amyotrophic lateral sclerosis (ALS). Indeed, exercise and other therapies that modulate kinases are effective at delaying ALS progression, preserving NMJs and maintaining motor function to increase the life quality of patients. Altogether, we review synaptic activity modulation of the BDNF/TrkB/PKC signaling to sustain NMJ function, its and other kinases’ disturbances in ALS and physical and molecular mechanisms to delay disease progression. MDPI 2019-12-05 /pmc/articles/PMC6953086/ /pubmed/31817487 http://dx.doi.org/10.3390/cells8121578 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Lanuza, Maria A.
Just-Borràs, Laia
Hurtado, Erica
Cilleros-Mañé, Víctor
Tomàs, Marta
Garcia, Neus
Tomàs, Josep
The Impact of Kinases in Amyotrophic Lateral Sclerosis at the Neuromuscular Synapse: Insights into BDNF/TrkB and PKC Signaling
title The Impact of Kinases in Amyotrophic Lateral Sclerosis at the Neuromuscular Synapse: Insights into BDNF/TrkB and PKC Signaling
title_full The Impact of Kinases in Amyotrophic Lateral Sclerosis at the Neuromuscular Synapse: Insights into BDNF/TrkB and PKC Signaling
title_fullStr The Impact of Kinases in Amyotrophic Lateral Sclerosis at the Neuromuscular Synapse: Insights into BDNF/TrkB and PKC Signaling
title_full_unstemmed The Impact of Kinases in Amyotrophic Lateral Sclerosis at the Neuromuscular Synapse: Insights into BDNF/TrkB and PKC Signaling
title_short The Impact of Kinases in Amyotrophic Lateral Sclerosis at the Neuromuscular Synapse: Insights into BDNF/TrkB and PKC Signaling
title_sort impact of kinases in amyotrophic lateral sclerosis at the neuromuscular synapse: insights into bdnf/trkb and pkc signaling
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6953086/
https://www.ncbi.nlm.nih.gov/pubmed/31817487
http://dx.doi.org/10.3390/cells8121578
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