Tau protein isoforms, phosphorylation and role in neurodegenerative disorders

Tau proteins belong to the family of microtubule-associated proteins. They are mainly expressed in neurons where they play an important role in the as sembly of tubulin monomers into microtubules to constitute the neuronal mic rotubules network. Microtubules are involved in maintaining the cell shape and serve as tracks for axonal transport. Tau proteins also establish some links between microtubules and other cytoskeletal elements or proteins. Tan proteins are translated from a single gene located on chromosome 17. Their expression is developmentally regulated by an alternative splicing mechani sm and six different isoforms exist in the human adult brain. Tau proteins are the major constituents of intraneuronal and glial fibrillar lesions des cribed in Alzheimer's disease and numerous neurodegenerative disorders refe rred to as 'tauopathies'. Molecular analysis has revealed that an abnormal phosphorylation might be one of the important events in the process leading to their aggregation. Moreover, a specific set of pathological tau protein s exhibiting a typical biochemical pattern, and a different regional and la minar distribution could characterize each of these disorders. Finally, a d irect correlation has been established between the progressive involvement of the neocortical areas and the increasing severity of dementia, suggestin g that pathological tau proteins are reliable marker of the neurodegenerati ve process. The recent discovery of tau gene mutations in frontotemporal de mentia with parkinsonism linked to chromosome 17 has reinforced the predomi nant role attributed to tau proteins in the pathogenesis of neurodegenerati ve disorders, and underlined the fact that distinct sets of tau isoforms ex pressed in different neuronal populations could lead to different pathologi es. (C) 2000 Elsevier Science B.V. All rights reserved.