Publications related to Molecular dissection of amyloid disaggregation by human HSP70

Method of preparation of amyloidogenic protein aggregates and uses thereof

The invention relates to methods for the preparation of method of preparation of Tau aggregates, including fibrils, fibrillar species, soluble and insoluble oligomeric species, new Tau aggregates and uses thereof. The invention further relates to the uses ...

2024

Targeting TDP-43 Proteinopathies in Neurodegeneration by its Native-State Stabilization

Lixin Yang

Preventing the misfolding or aggregation of TDP-43 is the most actively pursued disease-modifying strategy to treat amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. In our work, we provide proof of concept that native state stabili ...

EPFL2024

Autorepression of yeast Hsp70 cochaperones by intramolecular interactions involving their J-domains

Paolo De Los Rios, Bruno Claude Daniel Fauvet, Adélaïde Alice Mohr, Satyam Tiwari, Mathieu Rebeaud, Pierre Goloubinoff

The 70 kDa heat shock protein (Hsp70) chaperones control protein homeostasis in all ATP-containing cellular compartments. J-domain proteins (JDPs) coevolved with Hsp70s to trigger ATP hydrolysis and catalytically upload various substrate polypeptides in ne ...

Elsevier Science Inc2024

Distinct ultrastructural phenotypes of glial and neuronal alpha-synuclein inclusions in multiple system atrophy

Henning Paul-Julius Stahlberg, Amanda Jennifer Lewis, Domenic Burger, Marta Di Fabrizio, Carolin Böing

Multiple System Atrophy is characterized pathologically by the accumulation of alpha-synuclein (aSyn) into glial cytoplasmic inclusions (GCIs). The mechanism underlying the formation of GCIs is not well understood. In this study, correlative light and elec ...

2024

Synergetic Support of Cartilage Homeostasis via Coupled Thermal-Hydrostatic Pressure Stimuli

Yanheng Guo

Cartilage homeostasis, crucial for musculoskeletal function, is orchestrated by interconnected biophysical cues. In healthy cartilage, repetitive compressive loading not only elicits a range of mechanical stimuli but also induces a gradual transient temper ...

EPFL2024

Magic Angle Spinning Solid-State 13C Photochemically Induced Dynamic Nuclear Polarization by a Synthetic Donor-Chromophore-Acceptor System at 9.4 T

David Lyndon Emsley, Michael Allan Hope, Máté Visegrádi, Federico De Biasi

Solid-state photochemically induced dynamic nuclear polarization (photo-CIDNP) is a nuclear magnetic resonance spectroscopy technique in which nuclear spin hyperpolarization is generated upon optical irradiation of an appropriate donor-acceptor system. Unt ...

Amer Chemical Soc2024

Magnetic structure and magnetoelectric properties of the spin-flop phase in LiFePO4

Sofie Janas, Ellen Fogh, Paola Caterina Forino

We investigate the magnetic structure and magnetoelectric(ME) effect in the high -field phase of the antiferromagnet LiFePO 4 above the critical field of 31 T. A neutron diffraction study in pulsed magnetic fields reveals the propagation vector to be q = 0 ...

Amer Physical Soc2024

High brightness neutron source optimized for very high pulsed magnetic field experiments

Mina Akhyani

Conducting neutron scattering experiments in the presence of high pulsed magnetic fields, namely above 40 T, provides valuable information about the magnetic structures of materials. However, these experiments are challenging and time-consuming because the ...

EPFL2024

Deconstructing and Reconstructing the Complexity of Tau pathology

Galina Limorenko

This thesis consists of four Chapters unified by a singular theme â how do we develop disease models that faithfully reproduce the pathology seen in patients suffering from neurodegenerative disorders associated with the Tau protein, such as Alzheimerâ ...

EPFL2023

Recombinant Full-Length TDP-43 Oligomers Retain Their Ability to Bind RNAs, Are Not Toxic, and Do Not Seed TDP-43 Aggregation in Vitro

Hilal Lashuel, Lixin Yang, Yllza Jasiqi

TAR DNA-binding protein with 43 kD (TDP-43) is a partially disordered protein that misfolds and accumulates in the brains of patients affected by several neurodegenerative diseases. TDP-43 oligomers have been reported to form due to aberrant misfolding or ...

Amer Chemical Soc2023

Classification of patients with cardiac amyloidosis using machine learning models on Italian electronic clinical health records

Silvestro Micera, Sara Mazzucato

Amyloidosis refers to a range of medical conditions in which misshapen proteins accumulate in various organs and tissues, forming insoluble fibrils. Cardiac amyloidosis is frequently linked to the buildup of misfolded transthyretin (TTR) or immunoglobulin ...

IEEE2023

Discontinuous Galerkin methods for Fisher-Kolmogorov equation with application to a-synuclein spreading in Parkinson's disease

Alfio Quarteroni, Francesca Bonizzoni

This spreading of prion proteins is at the basis of brain neurodegeneration. This paper deals with the numerical modelling of the misfolding process of a-synuclein in Parkinson's disease. We introduce and analyse a discontinuous Galerkin method for the sem ...

Elsevier Science Sa2023

Effective Inhibition of TDP-43 Aggregation by Native State Stabilization

Hilal Lashuel, Lixin Yang, Yllza Jasiqi

Preventing the misfolding or aggregation of transactive response DNA binding protein with 43 kDa (TDP-43) is the most actively pursued disease-modifying strategy to treat amyotrophic lateral sclerosis and other neurodegenerative diseases. In this work, we ...

Wiley-VCH Verlag GmbH2024

Fast Self-Assembly Dynamics of a beta-Sheet Peptide Soft Material

Sandor Kasas, Charlotte Martin

Peptide-based hydrogels are promising biocompatible materials for wound healing, drug delivery, and tissue engineering applications. The physical properties of these nanostructured materials depend strongly on the morphology of the gel network. However, th ...

WILEY-V C H VERLAG GMBH2023

Why do we need so many proteins? A physical insight into the collaboration of Hsp70 and DnaJ

Adélaïde Alice Mohr

The Hsp70 cycle is a key element of protein homeostasis, which is essential to avoid protein aggregation and protein-related diseases. Despite many experimental observations of the interaction between Hsp70, its co-chaperone DnaJ and various substrates, li ...

EPFL2023

Hierarchy of the Components in Spray-Dried, Protein-Excipient Particles Using DNP-Enhanced NMR Spectroscopy

David Lyndon Emsley, Baptiste Busi, Pierrick Berruyer, Andrea Bertarello

Protein-based drugs are becoming increasingly important, but there are challenges associated with their formulation (for example, formulating stable inhalable aerosols while maintaining the proper long-term stability of the protein). Determining the morpho ...

Amer Chemical Soc2023

Development and validation of an expanded antibody toolset that captures alpha-synuclein pathological diversity in Lewy body diseases

Hilal Lashuel, Melek Firat Altay, Johannes Burtscher, Somanath Jagannath

The abnormal aggregation and accumulation of alpha-synuclein (aSyn) in the brain is a defining hallmark of synucleinopathies. Various aSyn conformations and post-translationally modified forms accumulate in pathological inclusions and vary in abundance amo ...

Nature Portfolio2023

Influence of DNP Polarizing Agents on Biochemical Processes: TEMPOL in Transient Ischemic Stroke

Lara Buscemi Estefanell, Mor-Miri Mishkovsky, Mario Gaetano Lepore, Jean-Noël Hyacinthe, Thanh Phong Kevin Lê

Hyperpolarization of 13C by dissolution dynamic nuclear polarization (dDNP) boosts the sensitivity of magnetic resonance spectroscopy (MRS), making possible the monitoring in vivo and in real time of the biochemical reactions of exogenously infused 13C-lab ...

2023

NMR Crystallography in the Big Data Era: New Methods and Applications Powered by Machine Learning

Manuel Cordova

Structure determination of materials is key to understanding their physical properties. While single-crystal X-ray diffraction is the gold standard for structures displaying long-range order, many materials of interest are polycrystalline and/or disordered ...

EPFL2023

Harmonization of multi-scanner in vivo magnetic resonance spectroscopy: ENIGMA consortium task group considerations

Cristina Ramona Cudalbu

Magnetic resonance spectroscopy is a powerful, non-invasive, quantitative imaging technique that allows for the measurement of brain metabolites that has demonstrated utility in diagnosing and characterizing a broad range of neurological diseases. Its impa ...

FRONTIERS MEDIA SA2023