Michele Vendruscolo

1 week ago | journals.plos.org | Christine Lim |Michele Vendruscolo

Fig 7. Central role of mid-stage regulatory proteins in the proteostasis network perturbations in AD. The functional interaction network of AD-associated proteostasis network genes (from all disease stages) are shown. Genes affected in the early stage are depicted as blue nodes; mid stage as beige nodes; and late stage as red nodes.

2 months ago | biorxiv.org | Christine Lim |John Hardy |Michele Vendruscolo

AbstractAmyloid plaques and neurofibrillary tangles are molecular hallmarks of Alzheimer's disease. According to the amyloid cascade hypothesis, aberrant Aβ and tau behaviours contribute synergistically to accelerate the Alzheimer's pathology. However, the complex molecular mechanisms linking Aβ and tau dysregulation remain to be fully characterised. To address this problem, we investigated the connection between Aβ and tau through the protein homeostasis (proteostasis) network.

Mar 4, 2025 | nature.com | Robert Horne |Sarah Sandler |Michele Vendruscolo

AbstractPowerful single-molecule approaches have been developed for the accurate measurement of protein oligomers, but they are often low throughput and limited to the measurement of specific systems. To overcome this problem, nanopore-based detection holds the promise of providing the high throughput, broad applicability, and accuracy necessary to characterize protein oligomers in a variety of contexts.

Aug 17, 2024 | nature.com | Catherine Xu |Georg Meisl |Ewa Andrzejewska |Georg Krainer |Irina Edu |Michele Vendruscolo | +1 more

AbstractOligomeric species arising during the aggregation of α-synuclein are implicated as a major source of toxicity in Parkinson’s disease, and thus a major potential drug target. However, both their mechanism of formation and role in aggregation are largely unresolved. Here we show that, at physiological pH and in the absence of lipid membranes, α-synuclein aggregates form by secondary nucleation, rather than simple primary nucleation, and that this process is enhanced by agitation.

Feb 5, 2024 | nature.com | Michele Vendruscolo

AbstractMany proteins self-assemble to form amyloid fibrils, which are highly organized structures stabilized by a characteristic cross-β network of hydrogen bonds. This process underlies a variety of human diseases and can be exploited to develop versatile functional biomaterials. Thus, protein self-assembly has been widely studied to shed light on the properties of fibrils and their intermediates.