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Luminescent-Conjugated Oligothiophene Probe Applications for Fluorescence Imaging of Pure Amyloid Fibrils and Protein Aggregates in Tissues

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Amyloid Proteins

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1779))

Abstract

Luminescent-conjugated oligo- and polythiophenes (LCOs and LCPs) are valuable tools for optical imaging of a plethora of protein aggregates associated with amyloidoses. Here, we outline updated protocols for the application of the anionic pentameric LCO, p-FTAA, for staining and hyperspectral imaging of protein aggregates in a variety of settings such as in vitro formed amyloid fibrils, ex vivo tissue sections, and whole brain Drosophila.

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References

  1. Sipe JD, Benson MD, Buxbaum JN et al (2016) Amyloid fibril proteins and amyloidosis: chemical identification and clinical classification International Society of Amyloidosis 2016 Nomenclature Guidelines. Amyloid 23:209–213

    Article  PubMed  CAS  Google Scholar 

  2. Bennhold H (1922) Eine specifische Amyloidfärbung mit Kongorot. Műnchener Med Wochenschrift 44:1537–1538

    Google Scholar 

  3. Divry P (1927) Etude histochimique des plaques seniles. J Neurol Psychiatry 27:643–657

    Google Scholar 

  4. Schütz AK, Soragni A, Hornemann S et al (2011) The amyloid-Congo red interface at atomic resolution. Angew Chem Int Ed Engl 50(26):5956–5960

    Article  PubMed  CAS  Google Scholar 

  5. Herrmann US, Schütz AK, Shirani H et al (2015) Structure-based drug design identifies polythiophenes as antiprion compounds. Sci Transl Med 7(299):299ra123

    Article  PubMed  CAS  Google Scholar 

  6. Nilsson KPR, Herland A, Hammarström P et al (2005) Conjugated polyelectrolytes – conformation sensitive optical probes for detection of amyloid fibril formation. Biochemistry 44:3718–3724

    Article  PubMed  CAS  Google Scholar 

  7. Nilsson KPR, Hammarström P, Ahlgren F et al (2006) Conjugated polyelectrolytes – conformation-sensitive optical probes for staining and characterization of amyloid deposits. Chembiochem 7:1096–1104

    Article  PubMed  CAS  Google Scholar 

  8. Nilsson KPR, Åslund A, Berg I et al (2007) Imaging distinct conformational states of amyloid-beta fibrils in Alzheimer’s disease using novel luminescent probes. ACS Chem Biol 2:553–560

    Article  PubMed  CAS  Google Scholar 

  9. Sigurdson CJ, Nilsson KPR, Hornemann S et al (2007) Prion strain discrimination using luminescent conjugated polymers. Nat Methods 12:1023–1030

    Article  CAS  Google Scholar 

  10. Sigurdson CJ, Nilsson KPR, Hornemann S et al (2009) De novo generation of a transmissible spongiform encephalopathy by mouse transgenesis. Proc Natl Acad Sci U S A 106:304–309

    Article  PubMed  Google Scholar 

  11. Nilsson KPR (2009) Small organic probes as amyloid specific ligands – past and recent molecular scaffolds. FEBS Lett 583:2593–2599

    Article  PubMed  CAS  Google Scholar 

  12. Åslund A, Sigurdson CJ, Klingstedt T et al (2009) Novel pentameric thiophene derivatives for in vitro and in vivo optical imaging of a plethora of protein aggregates in cerebral amyloidoses. ACS Chem Biol 4:673–684

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Nilsson KPR, Ikenberg K, Aslund Å et al (2010) Structural typing of systemic amyloidoses by luminescent-conjugated polymer spectroscopy. Am J Pathol 176:563–574

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Berg I, Nilsson KPR, Thor S et al (2010) Efficient imaging of amyloid deposits in Drosophila models of human amyloidoses. Nat Protoc 5:935–944

    Article  PubMed  CAS  Google Scholar 

  15. Hammarström P, Simon R, Nyström S et al (2010) A fluorescent pentameric thiophene derivative detects in vitro-formed prefibrillar protein aggregates. Biochemistry 49:6838–6845

    Article  PubMed  CAS  Google Scholar 

  16. Nilsson KPR, Joshi-Barr S, Winson O et al (2010) Prion strain interactions are highly selective. J Neurosci 30:12094–12102

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Bäck M, Appelqvist H, LeVine H 3rd et al (2016) Anionic oligothiophenes compete for binding of X-34 but not PIB to recombinant Aβ amyloid fibrils and Alzheimer’s disease brain-derived Aβ. Chemistry 22(51):18335–18338

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Klingstedt T, Aslund A, Simon RA et al (2011) Synthesis of a library of oligothiophenes and their utilization as fluorescent ligands for spectral assignment of protein aggregates. Org Biomol Chem 9(24):8356–8370

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Nyström S, Psonka-Antonczyk KM, Ellingsen PG et al (2013) Evidence for age-dependent in vivo conformational rearrangement within Aβ amyloid deposits. ACS Chem Biol 8(6):1128–1133

    Article  PubMed  CAS  Google Scholar 

  20. Sjölander D, Röcken C, Westermark P et al (2016) Establishing the fluorescent amyloid ligand h-FTAA for studying human tissues with systemic and localized amyloid. Amyloid 23(2):98–108

    Article  PubMed  CAS  Google Scholar 

  21. Magnusson K, Simon R, Sjölander D et al (2014) Multimodal fluorescence microscopy of prion strain specific PrP deposits stained by thiophene-based amyloid ligands. Prion 8(4):319–329

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Stabo-Eeg F, Lindgren M, Nilsson KPR et al (2007) Quantum efficiency and two-photon absorption cross-section of conjugated polyelectrolytes used for protein conformation measurements with applications on amyloid structures. Chem Phys 336:121–126

    Article  CAS  Google Scholar 

  23. Lindgren M, Glimsdal E, Åslund A et al (2010) Luminescence and two-photon absorption cross section of novel oligomeric luminescent conjugated polythiophenes for diagnostics of amyloid fibrils. Nonlin Opt Quantum Opt 40:241–251

    CAS  Google Scholar 

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Acknowledgment

This work was supported by the Swedish Research Council (P.H.), Linköping University (P.H., K.P.R.N., M.L.), The Swedish Foundation for Strategic Research (K.P.R.N.), and Göran Gustafsson Foundation (P.H.). We thank Maria Jonson for the spectral image of Drosophila brain and Daniel Sjölander for the images of TTR cardiac amyloid.

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Correspondence to Per Hammarström .

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Nilsson, K.P.R., Lindgren, M., Hammarström, P. (2018). Luminescent-Conjugated Oligothiophene Probe Applications for Fluorescence Imaging of Pure Amyloid Fibrils and Protein Aggregates in Tissues. In: Sigurdsson, E., Calero, M., Gasset, M. (eds) Amyloid Proteins. Methods in Molecular Biology, vol 1779. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7816-8_30

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  • DOI: https://doi.org/10.1007/978-1-4939-7816-8_30

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-7815-1

  • Online ISBN: 978-1-4939-7816-8

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