Repositori institucional URV
| URV's Author/s: | 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 |
| Author, as appears in the article.: | Just-Borras, Laia; Hurtado, Erica; Cilleros-Mane, Victor; Biondi, Olivier; Charbonnier, Frederic; Tomas, Marta; Garcia, Neus; Lanuza, Maria A; Tomas, Josep |
| Author's mail: | 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 |
| Author identifier: | 0000-0003-0473-3730 0000-0002-4151-1697 0000-0001-5690-9932 0000-0002-0406-0006 0000-0003-0473-3730 0000-0003-4795-4103 |
| Journal publication year: | 2019 |
| Publication Type: | Journal Publications |
| ISSN: | 08937648 |
| 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 |
| Papper original source: | Molecular Neurobiology. 56 (10): 6856-6872 |
| Abstract: | 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. |
| Article's DOI: | 10.1007/s12035-019-1550-1 |
| Link to the original source: | https://link.springer.com/article/10.1007%2Fs12035-019-1550-1 |
| Papper version: | info:eu-repo/semantics/submittedVersion |
| licence for use: | https://creativecommons.org/licenses/by/3.0/es/ |
| Department: | Ciències Mèdiques Bàsiques |
| Licence document URL: | https://repositori.urv.cat/ca/proteccio-de-dades/ |
| Thematic Areas: | 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 |
| Keywords: | 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 |
| Entity: | Universitat Rovira i Virgili |
| Record's date: | 2024-10-12 |
| First page: | 6856 |
| Last page: | 6872 |
| Journal volume: | 56 |
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