Biology subjects

Claessens, M. M. A. E.

Publications and source records attributed to Claessens, M. M. A. E..

3 recordsLinked to original sources

bioRxiv2023

SARS-CoV-2 N-protein induces the formation of composite α-synuclein/N-protein fibrils that transform into a strain of α-synuclein fibrils

The presence of deposits of alpha-synuclein fibrils in cells of the brain are a hallmark of several -synucleinopathies, including Parkinsons disease. As most disease cases are not familial, it is likely that external factors play a role in disease onset. One of the external factors that may influence disease onset are viral infections. It has recently been shown that in the presence of SARS-Cov-2 N-protein, S fibril formation is faster and proceeds in an unusual two-step aggregation process. Here, we show that faster fibril formation is not due to a SARS-CoV-2 N-protein-catalysed formation of an aggregation-prone nucleus. Instead, aggregation starts with the formation of a population of mixed S/N-protein fibrils with low affinity for S. After the depletion of N-protein, fibril formation comes to a halt, until a slow transformation to fibrils with characteristics of pure S fibril strains occurs. This transformation into a strain of S fibrils subsequently results in a second phase of fibril growth until a new equilibrium is reached. Our findings point at the possible relevance of fibril strain transformation in the cell-to-cell spread of the S pathology and disease onset.

biophysics↗

bioRxiv2022

Biomolecular condensates can both accelerate and suppress aggregation of α-synuclein

Biomolecular condensates present in cells can fundamentally affect the aggregation of amyloidogenic proteins and play a role in the regulation of this process. While liquid-liquid phase separation of amyloidogenic proteins by themselves can act as an alternative nucleation pathway, interaction of partly disordered aggregation-prone proteins with pre-existing condensates that act as localization centers could be a far more general mechanism of altering their aggregation behavior. Here, we show that so-called host biomolecular condensates can both accelerate and slow down amyloid formation. We study the amyloidogenic protein -synuclein and two truncated -synuclein variants in the presence of three types of condensates composed of non-aggregating peptides, RNA or ATP. Our results demonstrate that condensates can dramatically speed up amyloid formation when proteins localize to their interface. However, condensates can also significantly suppress aggregation by sequestering and stabilizing amyloidogenic proteins, thereby providing living cells with a possible protection mechanism against amyloid formation.

biophysics↗

bioRxiv2021

Interactions between SARS-CoV-2 N-protein and α-synuclein accelerate amyloid formation

First cases that point at a correlation between SARS-CoV-2 infections and the development of Parkinsons disease have been reported. Currently it is unclear if there also is a direct causal link between these diseases. To obtain first insights into a possible molecular relation between viral infections and the aggregation of -synuclein protein into amyloid fibrils characteristic for Parkinsons disease, we investigated the effect of the presence of SARS-CoV-2 proteins on -synuclein aggregation. We show, in test tube experiments, that SARS-CoV-2 S-protein has no effect on -synuclein aggregation while SARS-CoV-2 N-protein considerably speeds up the aggregation process. We observe the formation of multi-protein complexes, and eventually amyloid fibrils. Microinjection of N-protein in SHSY-5Y cells disturbed the -synuclein proteostasis and increased cell death. Our results point toward direct interactions between the N-protein of SARS-CoV-2 and -synuclein as molecular basis for the observed coincidence between SARS-CoV-2 infections and Parkinsonism.

biophysics↗