TY  - JOUR
AB  - The aggregation of proteins into amyloid fibers is linked to more than forty still incurable cellular and eurodegenerative diseases such as Parkinson’s disease (PD), multiple system atrophy, Alzheimer’s disease and type 2 diabetes, among thers. 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 eparation 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.
DA  - 2022
DO  - 10.3390/molecules27010088
KW  - protein aggregation
KW  - oligomer
KW  - α-synuclein
KW  - secondary structure
KW  - biophysics
KW  - model systems
LA  - eng
IS  - 1
PY  - 2022
T2  - Molecules
TI  - Implementing Complementary Approaches to Shape the Mechanism of α-Synuclein Oligomerization as a Model of Amyloid Aggregation
UR  - https://nbn-resolving.org/urn:nbn:de:0070-pub-29603256
Y2  - 2024-11-21T23:20:45
ER  -