Cell-free amplification of prions: Where do we stand?

Federico Angelo Cazzaniga, Chiara Maria Giulia De Luca, Edoardo Bistaffa, Alessandra Consonni, Giuseppe Legname, Giorgio Giaccone, Fabio Moda

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Neurodegenerative diseases (NDs) such as Alzheimer's disease (AD), Parkinson's disease (PD), atypical parkinsonisms, frontotemporal dementia (FTLD) and prion diseases are characterized by the accumulation of misfolded proteins in the central nervous system (CNS). Although the cause for the initiation of protein aggregation is not well understood, these aggregates are disease-specific. For instance, AD is characterized by the intraneuronal accumulation of tau and extracellular deposition of amyloid-β (Aβ), PD is marked by the intraneuronal accumulation of α-synuclein, many FTLD are associated with the accumulation of TDP-43 while prion diseases show aggregates of misfolded prion protein. Hence, misfolded proteins are considered disease-specific biomarkers and their identification and localization in the CNS, collected postmortem, is required for a definitive diagnosis. With the development of two innovative cell-free amplification techniques named Protein Misfolding Cyclic Amplification (PMCA) and Real-Time Quaking-Induced Conversion (RT-QuIC), traces of disease-specific biomarkers were found in CSF and other peripheral tissues (e.g., urine, blood, and olfactory mucosa) of patients with different NDs. These techniques exploit an important feature shared by many misfolded proteins, that is their ability to interact with their normally folded counterparts and force them to undergo similar structural rearrangements. Essentially, RT-QuIC and PMCA mimic in vitro the same pathological processes of protein misfolding which occur in vivo in a very rapid manner. For this reason, they have been employed for studying different aspects of protein misfolding but, overall, they seem to be very promising for the premortem diagnosis of NDs.

Original languageEnglish
Title of host publicationProgress in Molecular Biology and Translational Science
EditorsGiuseppe Legname
PublisherElsevier B.V.
Pages325-358
Number of pages34
ISBN (Print)9780128200025
DOIs
Publication statusPublished - 2020

Publication series

NameProgress in Molecular Biology and Translational Science
Volume175
ISSN (Print)1877-1173
ISSN (Electronic)1878-0814

Keywords

  • Blood
  • Cerebrospinal fluid
  • Early diagnosis
  • Misfolding
  • Neurodegenerative diseases
  • Olfactory mucosa
  • PMCA
  • RT-QuIC
  • Urine

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

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