Synthetic prions and other human neurodegenerative proteinopathies

Nhat Tran Thanh Le, Joanna Narkiewicz, Suzana Aulić, Giulia Salzano, Hoa Thanh Tran, Denis Scaini, Fabio Moda, Gabriele Giachin, Giuseppe Legname

Research output: Contribution to journalArticle

Abstract

Transmissible spongiform encephalopathies (TSE) are a heterogeneous group of neurodegenerative disorders. The common feature of these diseases is the pathological conversion of the normal cellular prion protein (PrPC) into a β-structure-rich conformer-termed PrPSc. The latter can induce a self-perpetuating process leading to amplification and spreading of pathological protein assemblies. Much evidence suggests that PrPSc itself is able to recruit and misfold PrPC into the pathological conformation. Recent data have shown that recombinant PrPC can be misfolded in vitro and the resulting synthetic conformers are able to induce the conversion of PrPC into PrPSc in vivo. In this review we describe the state-of-the-art of the body of literature in this field. In addition, we describe a cell-based assay to test synthetic prions in cells, providing further evidence that synthetic amyloids are able to template conversion of PrP into prion inclusions. Studying prions might help to understand the pathological mechanisms governing other neurodegenerative diseases. Aggregation and deposition of misfolded proteins is a common feature of several neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and other disorders. Although the proteins implicated in each of these diseases differ, they share a common prion mechanism. Recombinant proteins are able to aggregate in vitro into β-rich amyloid fibrils, sharing some features of the aggregates found in the brain. Several studies have reported that intracerebral inoculation of synthetic aggregates lead to unique pathology, which spread progressively to distal brain regions and reduced survival time in animals. Here, we review the prion-like features of different proteins involved in neurodegenerative disorders, such as α-synuclein, superoxide dismutase-1, amyloid-β and tau.

Original languageEnglish
Pages (from-to)25-37
Number of pages13
JournalVirus Research
Volume207
DOIs
Publication statusPublished - Sep 2 2015

Keywords

  • Neurodegenerative disorders
  • Prions
  • Protein misfolding diseases
  • Strains
  • Structural biology
  • Synthetic prions

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases
  • Cancer Research

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  • Cite this

    Le, N. T. T., Narkiewicz, J., Aulić, S., Salzano, G., Tran, H. T., Scaini, D., Moda, F., Giachin, G., & Legname, G. (2015). Synthetic prions and other human neurodegenerative proteinopathies. Virus Research, 207, 25-37. https://doi.org/10.1016/j.virusres.2014.10.020