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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 - imarina:5651484

Autor/es 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
Autor según el artículo:Just-Borras, Laia; Hurtado, Erica; Cilleros-Mane, Victor; Biondi, Olivier; Charbonnier, Frederic; Tomas, Marta; Garcia, Neus; Lanuza, Maria A; Tomas, Josep
Direcció de correo del 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 del 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
Año de publicación de la revista:2019
Tipo de publicación:Journal Publications
ISSN:08937648
Referencia 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
Referencia al articulo segun fuente origial:Molecular Neurobiology. 56 (10): 6856-6872
Resumen: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.
DOI del artículo:10.1007/s12035-019-1550-1
Enlace a la fuente original:https://link.springer.com/article/10.1007%2Fs12035-019-1550-1
Versión del articulo depositado:info:eu-repo/semantics/submittedVersion
Acceso a la licencia de uso:https://creativecommons.org/licenses/by/3.0/es/
Departamento:Ciències Mèdiques Bàsiques
URL Documento de licencia:https://repositori.urv.cat/ca/proteccio-de-dades/
Áreas temáticas: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
Palabras clave: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
Entidad:Universitat Rovira i Virgili
Fecha de alta del registro:2024-10-12
Página inicial:6856
Página final:6872
Volumen de revista:56
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