Open AccessInteractions between SARS-CoV-2 N-Protein and α-Synuclein Accelerate Amyloid Formation
Author(s) -
Slav A. Semerdzhiev,
Mohammad Amin Abolghassemi Fakhree,
Ine Segers-Nolten,
Christian Blum,
Mireille Maria Anna Elisabeth Claessens
Publication year - 2021
Publication title -
acs chemical neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.158
H-Index - 69
ISSN - 1948-7193
DOI - 10.1021/acschemneuro.1c00666
Subject(s) - proteostasis , protein aggregation , alpha synuclein , amyloid (mycology) , parkinsonism , chemistry , protein folding , biology , microbiology and biotechnology , parkinson's disease , disease , medicine , inorganic chemistry , pathology
First cases that point at a correlation between SARS-CoV-2 infections and the development of Parkinson's disease (PD) have been reported. Currently, it is unclear if there is also a direct causal link between these diseases. To obtain first insights into a possible molecular relation between viral infections and the aggregation of α-synuclein protein into amyloid fibrils characteristic for PD, we investigated the effect of the presence of SARS-CoV-2 proteins on α-synuclein aggregation. We show, in test tube experiments, that SARS-CoV-2 spike protein (S-protein) has no effect on α-synuclein aggregation, while SARS-CoV-2 nucleocapsid protein (N-protein) considerably speeds up the aggregation process. We observe the formation of multiprotein complexes and eventually amyloid fibrils. Microinjection of N-protein in SH-SY5Y cells disturbed the α-synuclein proteostasis and increased cell death. Our results point toward direct interactions between the N-protein of SARS-CoV-2 and α-synuclein as molecular basis for the observed correlation between SARS-CoV-2 infections and Parkinsonism.