• Open Access

Luminescent Conjugated Oligothiophenes for Sensitive Fluorescent Assignment of Protein Inclusion Bodies

Authors

  • Therése Klingstedt,

    1. Department of Chemistry, Linköping University, 581 83 Linköping (Sweden)
    Search for more papers by this author
  • Dr. Cristiane Blechschmidt,

    1. Department of Neuropathology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin (Germany)
    Search for more papers by this author
    • These authors contributed equally to this work.

  • Dr. Anna Nogalska,

    1. Department of Neurology, USC Neuromuscular Center, University of Southern California Keck School of Medicine, Good Samaritan Hospital, 637 S. Lucas Ave, Los Angeles, CA 90017-1912 (USA)
    Search for more papers by this author
    • These authors contributed equally to this work.

  • Dr. Stefan Prokop,

    1. Department of Neuropathology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin (Germany)
    Search for more papers by this author
  • Bo Häggqvist,

    1. Department of Neurology and Department of Clinical and Experimental Medicine, Division of Neurology, Faculty of Health Sciences, Linköping University, 581 83 Linköping (Sweden)
    Search for more papers by this author
  • Dr. Olof Danielsson,

    1. Department of Neurology and Department of Clinical and Experimental Medicine, Division of Neurology, Faculty of Health Sciences, Linköping University, 581 83 Linköping (Sweden)
    Search for more papers by this author
  • Prof. W. King Engel,

    1. Department of Neurology, USC Neuromuscular Center, University of Southern California Keck School of Medicine, Good Samaritan Hospital, 637 S. Lucas Ave, Los Angeles, CA 90017-1912 (USA)
    Search for more papers by this author
  • Prof. Valerie Askanas,

    1. Department of Neurology, USC Neuromuscular Center, University of Southern California Keck School of Medicine, Good Samaritan Hospital, 637 S. Lucas Ave, Los Angeles, CA 90017-1912 (USA)
    Search for more papers by this author
  • Prof. Frank L. Heppner,

    1. Department of Neuropathology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin (Germany)
    Search for more papers by this author
  • Dr. K. Peter R. Nilsson

    Corresponding author
    1. Department of Chemistry, Linköping University, 581 83 Linköping (Sweden)
    • Department of Chemistry, Linköping University, 581 83 Linköping (Sweden)
    Search for more papers by this author

Abstract

Small hydrophobic ligands identifying intracellular protein deposits are of great interest, as protein inclusion bodies are the pathological hallmark of several degenerative diseases. Here we report that fluorescent amyloid ligands, termed luminescent conjugated oligothiophenes (LCOs), rapidly and with high sensitivity detect protein inclusion bodies in skeletal muscle tissue from patients with sporadic inclusion body myositis (s-IBM). LCOs having a conjugated backbone of at least five thiophene units emitted strong fluorescence upon binding, and showed co-localization with proteins reported to accumulate in s-IBM protein inclusion bodies. Compared with conventional amyloid ligands, LCOs identified a larger fraction of immunopositive inclusion bodies. When the conjugated thiophene backbone was extended with terminal carboxyl groups, the LCO revealed striking spectral differences between distinct protein inclusion bodies. We conclude that 1) LCOs are sensitive, rapid and powerful tools for identifying protein inclusion bodies and 2) LCOs identify a wider range of protein inclusion bodies than conventional amyloid ligands.

Ancillary