info:eu-repo/semantics/article
Implementing complementary approaches to shape the mechanism of α-synuclein oligomerization as a model of amyloid aggregation
Registro en:
Giampà, Marco; Amundarain, María Julia; Herrera, Maria Georgina; Tonali, Nicolò; Dodero, Veronica Isabel; Implementing complementary approaches to shape the mechanism of α-synuclein oligomerization as a model of amyloid aggregation; Molecular Diversity Preservation International; Molecules; 27; 1; 1-2022; 1-21
1420-3049
CONICET Digital
CONICET
Autor
Giampà, Marco
Amundarain, María Julia
Herrera, Maria Georgina
Tonali, Nicolò
Dodero, Veronica Isabel
Resumen
The aggregation of proteins into amyloid fibers is linked to more than forty still incurable cellular and neurodegenerative diseases such as Parkinson’s disease (PD), multiple system atrophy, Alzheimer’s disease and type 2 diabetes, among others. The process of amyloid formation is a main feature of cell degeneration and disease pathogenesis. Despite being methodologically challenging, a complete understanding of the molecular mechanism of aggregation, especially in the early stages, is essential to find new biological targets for innovative therapies. Here, we reviewed selected examples on α-syn showing how complementary approaches, which employ different biophysical techniques and models, can better deal with a comprehensive study of amyloid aggregation. In addition to the monomer aggregation and conformational transition hypothesis, we reported new emerging theories regarding the self-aggregation of α-syn, such as the alpha-helix rich tetramer hypothesis, whose destabilization induce monomer aggregation; and the liquid-liquid phase separation hypothesis, which considers a phase separation of α-syn into liquid droplets as a primary event towards the evolution to aggregates. The final aim of this review is to show how multimodal methodologies provide a complete portrait of α-syn oligomerization and can be successfully extended to other protein aggregation diseases. Fil: Giampà, Marco. Norwegian University of Science and Technology; Noruega Fil: Amundarain, María Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Física del Sur. Universidad Nacional del Sur. Departamento de Física. Instituto de Física del Sur; Argentina Fil: Herrera, Maria Georgina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Ruhr Universität Bochum; Alemania Fil: Tonali, Nicolò. Universite Paris-Saclay; Fil: Dodero, Veronica Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universitat Bielefeld; Alemania