Exploring Amyloidogenicity of Clusterin: A Structural and Bioinformatics Analysis

  • Paraskevi L. Tsiolaki
  • Katerina C. Nastou
  • Nikolaos N. Louros
  • Stavros J. Hamodrakas
  • Vassiliki A. IconomidouEmail author
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 989)


Clusterin, a multitasking glycoprotein, is a protein highly conserved amongst mammals. In humans, Clusterin is mainly a secreted protein, described as an extracellular chaperone with the capability of interacting with a broad spectrum of molecules. In neurodegenerative diseases, such as Alzheimer’s disease, it is an amyloid associated protein, co-localized with fibrillar deposits in amyloid plaques in systemic or localized amyloidoses. An ‘aggregation-prone’ segment (NFHAMFQ) was located within the Clusterin α-chain sequence using AMYLPRED, a consensus method for the prediction of amyloid propensity, developed in our lab. This peptide was synthesized and was found to self-assemble into amyloid-like fibrils in vitro, as electron microscopy, X-ray fiber diffraction, Attenuated Total Reflectance Fourier-Transform Spectroscopy and Congo red staining studies reveal. All experimental results verify that this human Clusterin peptide-analogue, possesses high aggregation potency. Additional computational analysis highlighted novel and at the same time, unexplored features of human Clusterin.


Consensus algorithm Aggregation-prediction algorithm Clusterin “Aggregation-prone” peptides Alzheimer’s disease Neurodegenerative disease Protein network 



We thank the University of Athens for support. This project was financially supported by the Greek State Scholarships Foundation, through the Siemens Program: “IKY Fellowships of Excellence for Postgraduate Studies in Greece—Siemens Programme (2015–2017)”. We thank Associate Professor Ioannis Trougakos for pointing out to us the role of Clusterin in neurodegenerative diseases. We thank our collaborator Dr. Evangelia D. Chrysina for excellent assistance with the X-ray experiments and the Institute of Biology, Medicinal Chemistry and Biotechnology at the National Hellenic Research Foundation for hospitality. Finally, we thank Dr. Georgios E. Baltatzis and Prof. Efstratios S. Patsouris for excellent assistance with Transmission Electron Microscopy experiments in the Department of Pathology, at the Medical School of the University of Athens.


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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Paraskevi L. Tsiolaki
    • 1
  • Katerina C. Nastou
    • 1
  • Nikolaos N. Louros
    • 1
  • Stavros J. Hamodrakas
    • 1
  • Vassiliki A. Iconomidou
    • 1
    Email author
  1. 1.Section of Cell Biology and Biophysics, Department of BiologyNational and Kapodistrian University of AthensAthensGreece

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