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Intrinsically Disordered Proteins in the Neurodegenerative Processes: Formation of Tau Protein Paired Helical Filaments and Their Analysis

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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.

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ACKNOWLEDGMENTS

Support from the International Centre for Genetic Engineering and Biotechnology (ICGEB, grant CRP/SVK05-01) as well as from Scientific Grant Agency of the Ministry of Education of Slovak Republic and the Slovak Academy of Sciences (VEGA, grant 2/6172/26) is gratefully acknowledged.

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Authors and Affiliations

  1. Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, Slovakia

    Rostislav Skrabana & Michal Novak

  2. Axon Neuroscience Ltd., Vienna, Austria

    Rostislav Skrabana

  3. Institute of Molecular Biology, Slovak Academy of Sciences, Bratislava, Slovakia

    Jozef Sevcik

  4. Institute of Neuroimmunology, Slovak Academy of Sciences, Dubravska cesta 9, 845 10, Bratislava, Slovakia

    Michal Novak

Authors
  1. Rostislav Skrabana
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  2. Jozef Sevcik
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  3. Michal Novak
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Correspondence to Michal Novak.

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Dedicated to the late Peter Kontsek.

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Skrabana, R., Sevcik, J. & Novak, M. Intrinsically Disordered Proteins in the Neurodegenerative Processes: Formation of Tau Protein Paired Helical Filaments and Their Analysis. Cell Mol Neurobiol 26, 1083–1095 (2006). https://doi.org/10.1007/s10571-006-9083-3

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  • DOI: https://doi.org/10.1007/s10571-006-9083-3

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