Molecular dissection of the paired helical filament

M. Goedert, M. G. Spillantini, R. Jakes, R. A. Crowtherp, E. Vanmechelen, A. Probst, J. Götz, K. Bürki, P. Cohen

    Research output: Contribution to journalArticlepeer-review

    73 Citations (Scopus)

    Abstract

    Abundant neurofibrillary tangles, neuropil threads and plaque neurites constitute the neurofibrillary pathology of Alzheimer's disease. They form in the nerve cells that undergo degeneration in the disease where their regional distribution correlates with the degree of dementia. Each lesion contains the paired helical filament (PHF) as its major fibrous component. Recent work has shown that PHFs are composed of the microtubule-associated protein tau in a hyperphosphorylated state. PHF-tau is hyperphosphorylated on six adult brain tau isoforms. As a consequence, tau is unable to bind to microtubules and is believed to self-assemble into the PHF. Current evidence suggests that protein kinases or protein phosphatases with a specificity for serine/threonine-proline residues play an important role in the hyperphosphorylation of tau. Candidate protein kinases include mitogen-activated protein kinase, glycogen synthase kinase-3 and cyclin-dependent kinase 5, whereas the trimeric form of protein phosphatase 2A is a candidate phosphatase.

    Original languageEnglish
    Pages (from-to)325-334
    Number of pages10
    JournalNeurobiology of Aging
    Volume16
    Issue number3
    DOIs
    Publication statusPublished - 1995

    Keywords

    • Hyperphosphorylation
    • Neurofibrillary lesions
    • Paired helical filaments
    • Tau protein

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