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

© 2020 Elsevier Inc. All rights reserved..

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:175

Enthalten in:

Progress in molecular biology and translational science - 175(2020) vom: 18., Seite 325-358

Sprache:

Englisch

Beteiligte Personen:

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

Links:

Volltext

Themen:

Blood
Cerebrospinal fluid
Early diagnosis
Journal Article
Misfolding
Neurodegenerative diseases
Olfactory mucosa
PMCA
PrPSc Proteins
Prions
RT-QuIC
Review
Urine

Anmerkungen:

Date Completed 01.07.2021

Date Revised 01.07.2021

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/bs.pmbts.2020.08.005

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM315294965