Le transport axonal des neurofilaments et pathologie neurodégénérative.

Abstract

Les neurofilaments constituent l'un des principaux éléments du cytosquelette dans les cellules nerveuses. Les protéines qui les composent sont transportées dans l'axone par un transport lent. Certaines études suggéraient que les neurofilaments étaient transportés sous forme de polymères tandis que d'autres semblaient plutôt indiquer u n transport des sous-unités et leur assemblage sur des filaments stationnaires le long de l'axone. Récemment, on a visualisé in vivo le mouvement de neurofilaments marqués par u n composé fluorescent, qui apparaît comme une suite de mouvements rapides, bidirectionnels, des polymères interrompue par de longues pauses. Des moteurs de la famille des kinésines pourraient être impliqués. Des dérèglements dans l'assemblage et le transport des neurofilaments jouent sans doute un rôle dans des maladies neurodégénératives.

Neurofilaments are major cytoskeletal elements of nerve cells. Neurofilament proteins are synthesized in the cell body and move down the axon with the slow axonal transport component. For many years, the axonal transport of neurofilaments was a controversial issue. On one hand, some studies suggested that neurofilaments were transported as polymers whereas other experiments led to a model of subunit transport combined to their dynamic assembly with stationary filaments along the axon. Recently, a new approach led to the in vivo visualization of neurofilaments tagged with green fluorescent protein (GFP). The results indicate that the slow transport of neurofilaments result from the rapid movement of polymers interrupted by prolonged pauses. Moreover, the neurofilament transport is asynchronous and bidirectional, which explains the difficulties to observe their movements. Although the molecular mechanisms underlying neurofilament transport remain to be elucidated, there is emerging evidence of a role for motors of the kinesin family. Alterations in assembly and transport of neurofilaments could be involved in neurodegenerative diseases. Transgenic mouse studies showed that the formation of filamentous aggregates, especially in the axon, can sometimes provoque neuronal death.