107 Result(s)
within
Michele Vendruscolo
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Article
Open AccessPharmacological inhibition of α-synuclein aggregation within liquid condensates
Aggregated forms of α-synuclein constitute the major component of Lewy bodies, the proteinaceous aggregates characteristic of Parkinson’s disease. Emerging evidence suggests that α-synuclein aggregation may oc...
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Open AccessDiscovery of potent inhibitors of α-synuclein aggregation using structure-based iterative learning
Machine learning methods hold the promise to reduce the costs and the failure rates of conventional drug discovery pipelines. This issue is especially pressing for neurodegenerative diseases, where the develop...
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Open AccessMisfolded protein oligomers: mechanisms of formation, cytotoxic effects, and pharmacological approaches against protein misfolding diseases
The conversion of native peptides and proteins into amyloid aggregates is a hallmark of over 50 human disorders, including Alzheimer’s and Parkinson’s diseases. Increasing evidence implicates misfolded protein...
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Open AccessMaturation-dependent changes in the size, structure and seeding capacity of Aβ42 amyloid fibrils
Many 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 a...
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Open AccessSequence-based prediction of the intrinsic solubility of peptides containing non-natural amino acids
Non-natural amino acids are increasingly used as building blocks in the development of peptide-based drugs as they expand the available chemical space to tailor function, half-life and other key properties. Ho...
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Amyloid formation as a protein phase transition
The formation of amyloid fibrils is a general class of protein self-assembly behaviour, which is associated with both functional biology and the development of a number of disorders, such as Alzheimer and Park...
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Article
Open AccessCase report of a patient with unclassified tauopathy with molecular and neuropathological features of both progressive supranuclear palsy and corticobasal degeneration
Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are distinct clinicopathological subtypes of frontotemporal lobar degeneration. They both have atypical parkinsonism, and they usually h...
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Extracellular protein homeostasis in neurodegenerative diseases
The protein homeostasis (proteostasis) system encompasses the cellular processes that regulate protein synthesis, folding, concentration, trafficking and degradation. In the case of intracellular proteostasis,...
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Open AccessAmyloidogenic proteins in the SARS-CoV and SARS-CoV-2 proteomes
The phenomenon of protein aggregation is associated with a wide range of human diseases. Our knowledge of the aggregation behaviour of viral proteins, however, is still rather limited. Here, we investigated th...
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Open AccessProtein condensation diseases: therapeutic opportunities
Condensed states of proteins, including liquid-like membraneless organelles and solid-like aggregates, contribute in fundamental ways to the organisation and function of the cell. Perturbations of these states...
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Open AccessSmall soluble α-synuclein aggregates are the toxic species in Parkinson’s disease
Soluble α-synuclein aggregates varying in size, structure, and morphology have been closely linked to neuronal death in Parkinson’s disease. However, the heterogeneity of different co-existing aggregate specie...
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Open AccessMisfolded protein oligomers induce an increase of intracellular Ca2+ causing an escalation of reactive oxidative species
Alzheimer's disease is characterized by the accumulation in the brain of the amyloid β (Aβ) peptide in the form of senile plaques. According to the amyloid hypothesis, the aggregation process of Aβ also genera...
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Assessment of Therapeutic Antibody Developability by Combinations of In Vitro and In Silico Methods
Although antibodies have become the fastest-growing class of therapeutics on the market, it is still challenging to develop them for therapeutic applications, which often require these molecules to withstand s...
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Open AccessAn open-source automated PEG precipitation assay to measure the relative solubility of proteins with low material requirement
The solubility of proteins correlates with a variety of their properties, including function, production yield, pharmacokinetics, and formulation at high concentrations. High solubility is therefore a key requ...
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Article
Open AccessThe Hsc70 disaggregation machinery removes monomer units directly from α-synuclein fibril ends
Molecular chaperones contribute to the maintenance of cellular protein homoeostasis through assisting de novo protein folding and preventing amyloid formation. Chaperones of the Hsp70 family can further disagg...
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Open AccessThe Amyloid-β Pathway in Alzheimer’s Disease
Breakthroughs in molecular medicine have positioned the amyloid-β (Aβ) pathway at the center of Alzheimer’s disease (AD) pathophysiology. While the detailed molecular mechanisms of the pathway and the spatial-...
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Article
Open AccessA maximum caliber approach for continuum path ensembles
The maximum caliber approach implements the maximum entropy principle for trajectories by maximizing a path entropy under external constraints. The maximum caliber approach can be applied to a diverse set of e...
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A mistranslation-prone transcriptome underlying polyglutamine expansion diseases
We propose a mechanism underlying polyglutamine (polyQ) repeat expansion diseases, in which the translation of expanded CAG codon repeats leads to translation stress. The stress is generated by depletion of th...
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Open AccessPublisher Correction: Two human metabolites rescue a C. elegans model of Alzheimer’s disease via a cytosolic unfolded protein response
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Open AccessExogenous misfolded protein oligomers can cross the intestinal barrier and cause a disease phenotype in C. elegans
Misfolded protein oligomers are increasingly recognized as highly cytotoxic agents in a wide range of human disorders associated with protein aggregation. In this study, we assessed the possible uptake and result...
