1. Synthetic prions and other human neurodegenerative proteinopathies
- Author
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Gabriele Giachin, Suzana Aulic, Hoa Thanh Tran, Nhat Tran Thanh Le, Fabio Moda, Denis Scaini, Giulia Salzano, Giuseppe Legname, Joanna Narkiewicz, Le, Nhat Tran Thanh, Narkiewicz, Joanna, Aulic, Suzana, Salzano, Giulia, Tran, Hoa Thanh, Scaini, Deni, Moda, Fabio, Giachin, Gabriele, and Legname, Giuseppe
- Subjects
Cancer Research ,Protein Folding ,Prions ,animal diseases ,Cell ,SOD1 ,Strains ,Infectious Disease ,Biology ,Settore BIO/09 - Fisiologia ,law.invention ,Strain ,In vivo ,law ,Synthetic prion ,Virology ,medicine ,Animals ,Humans ,Amyotrophic lateral sclerosis ,Neurodegenerative disorders ,Protein misfolding diseases ,Structural biology ,Synthetic prions ,Neurodegenerative Diseases ,Proteins ,Infectious Diseases ,Medicine (all) ,Neurodegenerative Disease ,Animal ,Protein ,Neurodegenerative disorder ,Protein misfolding disease ,medicine.disease ,In vitro ,nervous system diseases ,Cell biology ,medicine.anatomical_structure ,Recombinant DNA ,Prion ,Protein folding ,Human - 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 (PrP(C)) into a β-structure-rich conformer-termed PrP(Sc). The latter can induce a self-perpetuating process leading to amplification and spreading of pathological protein assemblies. Much evidence suggests that PrP(Sc) itself is able to recruit and misfold PrP(C) into the pathological conformation. Recent data have shown that recombinant PrP(C) can be misfolded in vitro and the resulting synthetic conformers are able to induce the conversion of PrP(C) into PrP(Sc)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.
- Published
- 2015