Author, as appears in the article.: Just-Borràs L, Hurtado E, Cilleros-Mañé V, Biondi O, Charbonnier F, Tomàs M, Garcia N, Lanuza MA, Tomàs J

Department: Ciències Mèdiques Bàsiques

URV's Author/s: Cilleros Mañé, Víctor / Garcia Sancho, Maria de les Neus / Just Borràs, Laia / Lanuza Escolano, María Angel / Tomás Ferré, José Maria / Tomas Marginet, Marta

Keywords: Trkb Snap-25 Skeletal muscle Pkc Pka Nmj Munc18-1 Bdnf Als

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.

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

licence for use: https://creativecommons.org/licenses/by/3.0/es/

ISSN: 08937648

Author's mail: victor.cilleros@urv.cat marta.tomas@urv.cat mariaangel.lanuza@urv.cat laia.just@urv.cat josepmaria.tomas@urv.cat victor.cilleros@urv.cat

Author identifier: 0000-0001-5690-9932 0000-0002-4151-1697 0000-0003-4795-4103 0000-0003-0473-3730 0000-0002-0406-0006 0000-0001-5690-9932

Last page: 6872

Record's date: 2023-09-23

Journal volume: 56

Papper version: info:eu-repo/semantics/submittedVersion

Link to the original source: https://link.springer.com/article/10.1007%2Fs12035-019-1550-1

Licence document URL: http://repositori.urv.cat/ca/proteccio-de-dades/

Papper original source: Molecular Neurobiology. 56 (10): 6856-6872

APA: Just-Borràs L, Hurtado E, Cilleros-Mañé V, Biondi O, Charbonnier F, Tomàs M, Garcia N, Lanuza MA, Tomàs J (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

Article's DOI: 10.1007/s12035-019-1550-1

Entity: Universitat Rovira i Virgili

Journal publication year: 2019

First page: 6856

Publication Type: Journal Publications