Intrinsically disordered proteins in the neurodegenerative processes: Formation of tau protein paired helical filaments and their analysis

被引：66
作者：
Rostislav Skrabana [1 ]
Jozef Sevcik [2 ]
Michal Novak [3 ]
机构：
[1] Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava
[2] Axon Neuroscience Ltd., Vienna
[3] Institute of Molecular Biology, Slovak Academy of Sciences, Bratislava
[4] Institute of Neuroimmunology, Slovak Academy of Sciences, 845 10 Bratislava
来源：
Cellular and Molecular Neurobiology | 2006年 / 26卷 / 7期
关键词：
Alzheimer's disease; Intrinsically disordered proteins; Monoclonal antibody; Neurodegeneration; Neurofibrillary pathology; Paired helical filaments; Tau protein;
D O I：
10.1007/s10571-006-9083-3
中图分类号：
学科分类号：
摘要：
1. Several intrinsically disordered proteins (IDPs) play principal role in the neurodegenerative processes of various types. Among them, α-synuclein is involved in Parkinson's disease, prion protein in transmissible spongiform encephalopathies, and tau protein in Alzheimer's disease (AD) and related tauopathies. Neuronal damage in AD is accompanied by the presence of tau protein fibrils composed of paired helical filaments (PHF). 2. Tau protein represents a typical IDP. IDPs do not exhibit any stable secondary structure in the free form, but they are able to fold after binding to targets and contain regions with large propensity to adopt a defined type of secondary structure. Binding-folding event at tau protein leading to PHF generation is believed to happen in the course of tauopathies. 3. Detailed molecular topology of PHF formation is unknown. There are evidences about the cross-beta structure in PHF core; however the precise arrangement of the tau polypeptide chain is unclear. In this review we summarize current attempts at in vitro PHF reconstruction and the development of methods for PHF structure determination. The emphasis is put on the monoclonal antibodies used as structural molecular probes for research on the role of IDPs in pathogenesis of neurodegenerative diseases. © 2006 Springer Science+Business Media, Inc.
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页码：1085 / 1097
页数：12
相关论文
共 101 条
  • [1] Abraha A., Ghoshal N., Gamblin T.C., Cryns V., Berry R.W., Kuret J., Binder L.I., C-terminal inhibition of tau assembly in vitro and in Alzheimer's disease, J. Cell Sci., 113, 21, pp. 3737-3745, (2000)
  • [2] Ackmann M., Wiech H., Mandelkow E., Nonsaturable binding indicates clustering of tau on the microtubule surface in a paired helical filament-like conformation, J. Biol. Chem., 275, pp. 30335-30343, (2000)
  • [3] Alonso A., Mederlyova A., Novak M., Grundke-Iqbal I., Iqbal K., Promotion of hyperphosphorylation by frontotemporal dementia tau mutations, J. Biol. Chem., 279, pp. 34873-34881, (2004)
  • [4] Alonso A., Zaidi T., Novak M., Grundke-Iqbal I., Iqbal K., Hyperphosphorylation induces self-assembly of tau into tangles of paired helical filaments/straight filaments, Proc. Natl. Acad. Sci. U.S.A., 98, pp. 6923-6928, (2001)
  • [5] Baldwin R.L., Zimm B.H., Are denatured proteins ever random coils?, Proc. Natl. Acad. Sci. U.S.A., 97, pp. 12391-12392, (2000)
  • [6] Barghorn S., Davies P., Mandelkow E., Tau paired helical filaments from Alzheimer's disease brain and assembled in vitro are based on beta-structure in the core domain, Biochemistry, 43, pp. 1694-1703, (2004)
  • [7] Barghorn S., Mandelkow E., Toward a unified scheme for the aggregation of tau into Alzheimer paired helical filaments, Biochemistry, 41, pp. 14885-14896, (2002)
  • [8] Berriman J., Serpell L.C., Oberg K.A., Fink A.L., Goedert M., Crowther R.A., Tau filaments from human brain and from in vitro assembly of recombinant protein show cross-beta structure, Proc. Natl. Acad. Sci. U.S.A., 100, pp. 9034-9038, (2003)
  • [9] Berry R.W., Abraha A., Lagalwar S., Lapointe N., Gamblin T.C., Cryns V.L., Binder L.I., Inhibition of tau polymerization by its carboxy-terminal caspase cleavage fragment, Biochemistry, 42, pp. 8325-8331, (2003)
  • [10] Braak H., Braak E., Neuropathological stageing of Alzheimer-related changes, Acta. Neuropathol. (Berl.), 82, pp. 239-259, (1991)
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