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Cell adhesion molecules at the nodal complex in health and disease| old_uid | 10292 |
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| title | Cell adhesion molecules at the nodal complex in health and disease |
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| start_date | 2015/11/12 |
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| schedule | 14h |
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| online | no |
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| location_info | salle 03 |
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| details | Invité par Catherine Lubetzki |
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| summary | The high density of voltage-gated sodium (Nav) channels at the nodes of Ranvier allows the rapid saltatory propagation of the action potentials along the axons. Cell adhesion molecules play an important function in the formation of the node and of the paranodal regions which flank the nodes. The complex gliomedin/NrCAM/neurofascin-186 is crucial for the initial aggregation of Nav channels at hemi-nodes. In addition, the complex Caspr1/contactin-1/neurofascin-155 dictates the formation of the paranodal axo-glial complex and participates to the formation of the nodes. In a recent study, we demonstrated that the node of Ranvier is the primary site of the immune attack in patients with Guillain-Barré syndrome (GBS) or chronic inflammatory demyelinating polyneuropathy (CIDP). GBS and CIDP are groups of neuropathies that affect peripheral nerves. We found that a subset of CIDP patients with specific clinical features present antibodies directed against contactin-1 or neurofascin-155. Of interest these antibodies are mostly of the IgG4 isotype, a subclass that is believed to be anti-inflammatory. These data strongly suggest that IgG4 anti-paranodal proteins are pathogenic, however, this has not yet been proven. Using animal models, we demonstrated that the passive transfer of IgG4 against contactin-1 induced a chronic progressive pathology associated with conduction loss. These animals did not show signs of immune infiltration, demyelination, or axonal degeneration. Rather, the passive transfer of the IgG4 mediated a selective alteration of the paranodal Caspr1/contactin-1/neurofascin-155 complex predominantly in small motor axons. Using intraneural injections, we further show that anti-contactin-1 IgG4 have the potency to penetrate the paranodal segments which normally form a barrier to the lateral diffusion of particles. These results pinpoint that IgG4 to paranodal proteins can dismantle the paranodal complex and lead to conduction defects. Cell adhesion molecules thus play important function in myelin physiology and are reliable biomarkers in human inflammatory neuropathies. |
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| responsibles | Oliviero |
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