Calcium signaling pathways mediating synaptic potentiation triggered by amyotrophic lateral sclerosis IgG in motor nerve terminals
Sporadic amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects particularly motoneurons. Several pieces of evidence suggested the involvement of autoimmune mechanisms mediated by antibodies in ALS. However, the significance of those antibodies in the disease and the underly...
| Autores: | , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2006 |
| País: | Argentina |
| Institución: | Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales |
| Repositorio: | Biblioteca Digital (UBA-FCEN) |
| Idioma: | inglés |
| OAI Identifier: | paperaa:paper_02706474_v26_n10_p2661_Pagani |
| Acceso en línea: | http://hdl.handle.net/20.500.12110/paper_02706474_v26_n10_p2661_Pagani |
| Access Level: | acceso abierto |
| Palabra clave: | Calcium channels Calcium homeostasis alteration IP3R Phospholipase C RyR Signaling mechanisms calcium calcium channel N type calcium ion immunoglobulin G inositol trisphosphate neurotransmitter phospholipase C proteinase ryanodine receptor adult aged amyotrophic lateral sclerosis animal tissue antigen antibody reaction article autoimmunity calcium signaling calcium transport clinical article controlled study degenerative disease enzyme activity human immune response immunoreactivity male motoneuron mouse nerve ending neuromodulation neurotransmitter release nonhuman presynaptic membrane priority journal receptor upregulation synaptic potential synaptic transmission Adult Aged Amyotrophic Lateral Sclerosis Animals Calcium Calcium Channel Blockers Calcium Channels Calcium Channels, N-Type Calcium Signaling Dose-Response Relationship, Radiation Drug Interactions Electric Stimulation Enzyme Inhibitors Evoked Potentials Female Humans Immunoglobulin G Immunohistochemistry Immunoprecipitation Inositol 1,4,5-Trisphosphate Receptors Male Mice Middle Aged Muscle Fibers Neuromuscular Junction Neurotransmitter Agents omega-Conotoxin GVIA Presynaptic Terminals Receptors, Cytoplasmic and Nuclear Ryanodine Receptor Calcium Release Channel Statistics Synaptic Transmission Time Factors |
| Sumario: | Sporadic amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects particularly motoneurons. Several pieces of evidence suggested the involvement of autoimmune mechanisms mediated by antibodies in ALS. However, the significance of those antibodies in the disease and the underlying mechanisms are unknown. Here we showed that IgG purified from a group of sporadic ALS patients, but not familial ALS patients, specifically interact with the presynaptic membrane of motoneurons through an antigen-antibody interaction and modulated synaptic transmission. Immunoreactivity against nerve terminals showed strong correlation with synaptic modulation ability. In addition, several controls have ruled out the possibility for this synaptic modulation to be mediated through proteases or nonspecific effects. Effective IgG potentiated both spontaneous and asynchronous transmitter release. Application of pharmacological inhibitors suggested that activation of this increased release required a nonconstitutive Ca2+ influx through N-type (Ca v2.2) channels and phospholipase C activity and that activation of IP3 and ryanodine receptors were necessary to both activate and sustain the increased release. Consistent with the notion that ALS is heterogeneous disorder, our results reveal that, in ∼50% of ALS patients, motor nerve terminals constitutes a target for autoimmune response. Copyright © 2006 Society for Neuroscience. |
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