Articles producció científica> Ciències Mèdiques Bàsiques

Overview of Impaired BDNF Signaling, Their Coupled Downstream Serine-Threonine Kinases and SNARE/SM Complex in the Neuromuscular Junction of the Amyotrophic Lateral Sclerosis Model SOD1-G93A Mice

  • Dades identificatives

    Identificador: imarina:5651484
    Autors:
    Just-Borras, LaiaHurtado, EricaCilleros-Mane, VictorBiondi, OlivierCharbonnier, FredericTomas, MartaGarcia, NeusLanuza, Maria ATomas, Josep
    Resum:
    Amyotrophic lateral sclerosis (ALS) is a chronic neurodegenerative disease characterized by progressive motor weakness. It is accepted that it is caused by motoneuron degeneration leading to a decrease in muscle stimulation. However, ALS is being redefined as a distal axonopathy, in that neuromuscular junction dysfunction precedes and may even influence motoneuron loss. In this synapse, several metabotropic receptor-mediated signaling pathways converge on effector kinases that phosphorylate targets that are crucial for synaptic stability and neurotransmission quality. We have previously shown that, in physiological conditions, nerve-induced muscle contraction regulates the brain-derived neurotrophic factor/tropomyosin-related kinase B (BDNF/TrkB) signaling to retrogradely modulate presynaptic protein kinases PKC and PKA, which are directly involved in the modulation of acetylcholine release. In ALS patients, the alteration of this signaling may significantly contribute to a motor impairment. Here, we investigate whether BDNF/TrkB signaling, the downstream PKC (cPKCβI, cPKCα, and nPKCε isoforms), and PKA (regulatory and catalytic subunits) and some SNARE/SM exocytotic machinery proteins (Munc18-1 and SNAP-25) are altered in the skeletal muscle of pre- and symptomatic SOD1-G93A mice. We found that this pathway is strongly affected in symptomatic ALS mice muscles including an unbalance between (I) BDNF and TrkB isoforms, (II) PKC isoforms and PKA subunits, and (III) Munc18-1 and SNAP-25 phosphorylation ratios. Changes in TrkB.T1 and cPKCβI are precociously observed in presymptomatic mice. Altogether, several of these molecular alterations can be partly associated with the known fast-to-slow motor unit transition during the disease process but others can be related with the
  • Altres:

    Autor segons l'article: Just-Borras, Laia; Hurtado, Erica; Cilleros-Mane, Victor; Biondi, Olivier; Charbonnier, Frederic; Tomas, Marta; Garcia, Neus; Lanuza, Maria A; Tomas, Josep
    Departament: Ciències Mèdiques Bàsiques
    Autor/s de la URV: Cilleros Mañé, Víctor / Garcia Sancho, Maria de les Neus / Hurtado Caballero, Erica / Just Borràs, Laia / Lanuza Escolano, María Angel / Tomás Ferré, José Maria / Tomas Marginet, Marta
    Paraules clau: Trkb Superoxide dismutase-1 Spinal cord Snare proteins Snap-25 Skeletal muscle Signal transduction Receptors, nerve growth factor Protein serine-threonine kinases Pkc Pka Nmj Neuromuscular junction Nerve growth factors Muscles Munc18-1 Motor neurons Models, biological Mice, transgenic Male Disease models, animal Catalytic domain Brain-derived neurotrophic factor Bdnf Animals Amyotrophic lateral sclerosis Als
    Resum: Amyotrophic lateral sclerosis (ALS) is a chronic neurodegenerative disease characterized by progressive motor weakness. It is accepted that it is caused by motoneuron degeneration leading to a decrease in muscle stimulation. However, ALS is being redefined as a distal axonopathy, in that neuromuscular junction dysfunction precedes and may even influence motoneuron loss. In this synapse, several metabotropic receptor-mediated signaling pathways converge on effector kinases that phosphorylate targets that are crucial for synaptic stability and neurotransmission quality. We have previously shown that, in physiological conditions, nerve-induced muscle contraction regulates the brain-derived neurotrophic factor/tropomyosin-related kinase B (BDNF/TrkB) signaling to retrogradely modulate presynaptic protein kinases PKC and PKA, which are directly involved in the modulation of acetylcholine release. In ALS patients, the alteration of this signaling may significantly contribute to a motor impairment. Here, we investigate whether BDNF/TrkB signaling, the downstream PKC (cPKCβI, cPKCα, and nPKCε isoforms), and PKA (regulatory and catalytic subunits) and some SNARE/SM exocytotic machinery proteins (Munc18-1 and SNAP-25) are altered in the skeletal muscle of pre- and symptomatic SOD1-G93A mice. We found that this pathway is strongly affected in symptomatic ALS mice muscles including an unbalance between (I) BDNF and TrkB isoforms, (II) PKC isoforms and PKA subunits, and (III) Munc18-1 and SNAP-25 phosphorylation ratios. Changes in TrkB.T1 and cPKCβI are precociously observed in presymptomatic mice. Altogether, several of these molecular alterations can be partly associated with the known fast-to-slow motor unit transition during the disease process but others can be related with the initial disease pathogenesis.
    Àrees temàtiques: Saúde coletiva Química Odontología Nutrição Neurosciences Neuroscience (miscellaneous) Neurology Medicina veterinaria Medicina iii Medicina ii Medicina i Materiais Interdisciplinar Farmacia Ensino Engenharias iv Engenharias ii Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Ciências ambientais Cellular and molecular neuroscience Biotecnología Biodiversidade Administração pública e de empresas, ciências contábeis e turismo
    Accès a la llicència d'ús: https://creativecommons.org/licenses/by/3.0/es/
    ISSN: 08937648
    Adreça de correu electrònic de l'autor: laia.just@urv.cat marta.tomas@urv.cat erica.hurtado@urv.cat victor.cilleros@alumni.urv.cat josepmaria.tomas@urv.cat laia.just@urv.cat mariaangel.lanuza@urv.cat
    Identificador de l'autor: 0000-0003-0473-3730 0000-0002-4151-1697 0000-0001-5690-9932 0000-0002-0406-0006 0000-0003-0473-3730 0000-0003-4795-4103
    Pàgina final: 6872
    Data d'alta del registre: 2024-10-12
    Volum de revista: 56
    Versió de l'article dipositat: info:eu-repo/semantics/submittedVersion
    Enllaç font original: https://link.springer.com/article/10.1007%2Fs12035-019-1550-1
    URL Document de llicència: https://repositori.urv.cat/ca/proteccio-de-dades/
    Referència a l'article segons font original: Molecular Neurobiology. 56 (10): 6856-6872
    Referència de l'ítem segons les normes APA: Just-Borras, Laia; Hurtado, Erica; Cilleros-Mane, Victor; Biondi, Olivier; Charbonnier, Frederic; Tomas, Marta; Garcia, Neus; Lanuza, Maria A; Tomas, (2019). Overview of Impaired BDNF Signaling, Their Coupled Downstream Serine-Threonine Kinases and SNARE/SM Complex in the Neuromuscular Junction of the Amyotrophic Lateral Sclerosis Model SOD1-G93A Mice. Molecular Neurobiology, 56(10), 6856-6872. DOI: 10.1007/s12035-019-1550-1
    DOI de l'article: 10.1007/s12035-019-1550-1
    Entitat: Universitat Rovira i Virgili
    Any de publicació de la revista: 2019
    Pàgina inicial: 6856
    Tipus de publicació: Journal Publications
  • Paraules clau:

    Cellular and Molecular Neuroscience,Neurology,Neuroscience (Miscellaneous),Neurosciences
    Trkb
    Superoxide dismutase-1
    Spinal cord
    Snare proteins
    Snap-25
    Skeletal muscle
    Signal transduction
    Receptors, nerve growth factor
    Protein serine-threonine kinases
    Pkc
    Pka
    Nmj
    Neuromuscular junction
    Nerve growth factors
    Muscles
    Munc18-1
    Motor neurons
    Models, biological
    Mice, transgenic
    Male
    Disease models, animal
    Catalytic domain
    Brain-derived neurotrophic factor
    Bdnf
    Animals
    Amyotrophic lateral sclerosis
    Als
    Saúde coletiva
    Química
    Odontología
    Nutrição
    Neurosciences
    Neuroscience (miscellaneous)
    Neurology
    Medicina veterinaria
    Medicina iii
    Medicina ii
    Medicina i
    Materiais
    Interdisciplinar
    Farmacia
    Ensino
    Engenharias iv
    Engenharias ii
    Ciências biológicas iii
    Ciências biológicas ii
    Ciências biológicas i
    Ciências ambientais
    Cellular and molecular neuroscience
    Biotecnología
    Biodiversidade
    Administração pública e de empresas, ciências contábeis e turismo
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