Protéines TAU et maladies neurologiques.

Abstract

Les six isoformes des protéines Tau, synthétisées essentiellement au niveau des neurones, jouent un rôle important dans l'assemblage des microtubules et ainsi dans la formation des axones. L'hyperphosphorylation des protéines Tau au sein des inclusions cellulaires, caractéristiques de diverses maladies neurodégénératives, pourrait témoigner d'un déséquilibre entre kinases et phosphatases. Cette hyperphosphorylation modifie le transport axonal mais son rôle exact dans la mort neuronale est encore inconnu. Les études biochimiques des protéines Tau cérébrales couplées aux études immunohistochimiques utilisant des anticorps anti-Tau ont permis d'améliorer le diagnostic neuropathologique des affections neurodégénératives .

Tau proteins are neuronal microtubule-associated proteins, the expression of which in 6 isoforms is developmentally regulated. They are the major component of some neuronal inclusions, for example the neurofibrillar tangles (NFT) that, in neuropathological studies, characterize some neurodegenerative diseases. The biochemical abnormalities of Tau proteins in these histopathological lesions vary according to the diseases; one of these abnormalities is the hyperphosphorylation state of Tau and could result from a modified balance between kinase and phosphatase activity. Hyperphosphorylated Tau proteins become unable to bind microtubules and could disrupt axonal transport. However, the exact role of the biochemical abnormalities of the Tau proteins, among other neuronal or glial proteins, in the degeneration of neurons remains unknown: a direct role or an aspecific response of the neuron to various agressions? Finally if Tau proteins seem powerful biochemical and immunohistopathological markers of the neuro-degenerating process, their measurement in the cerebrospinal fluid cannot yet be used for the diagnosis of Alzheimer's disease. [References: 69]