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In Vivo Longitudinal (1)H MRS Study of Transgenic Mouse Models of Prion Disease in the Hippocampus and Cerebellum at 14.1 T

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Ultrafast photoinduced processes in metal - containing molecular complexes and in proteins

Roberto Monni

The aim of this thesis is to investigate the ultrafast inter¿ and intra¿molecular processes, occurring in both metal¿containing molecular complexes and in proteins, by means of ultrafast Transient Absorption (TA) spectroscopy. The first part of the thesis ...

EPFL2015

Molecular reconstruction and simulation of the Neuron-Glia-Vasculature system

Polina Shichkova

The outstanding information processing capacity of the brain relies on numerous molecular mechanisms. It is an extremely energy-expensive function, which involves specialization and collaboration of different cell types. A common framework to study the com ...

EPFL2023

The Protein-disulfide Isomerase ERp57 Regulates the Steady-state Levels of the Prion Protein

Maurizio Molinari

Although the accumulation of a misfolded and protease-resistant form of the prion protein (PrP) is a key event in prion pathogenesis, the cellular factors involved in its folding and quality control are poorly understood. PrP is a glycosylated and disulfid ...

Amer Soc Biochemistry Molecular Biology Inc2015

A novel UGGT1 and p97-dependent checkpoint for native ectodomains with ionizable intramembrane residue

Maurizio Molinari

Only native polypeptides are released from the endoplasmic reticulum (ER) to be transported at the site of activity. Persistently misfolded proteins are retained and eventually selected for ER-associated degradation (ERAD). The paradox of a structure-based ...

Amer Soc Cell Biology2015

alpha-Synuclein strains cause distinct synucleinopathies after local and systemic administration

Michele Giugliano

Misfolded protein aggregates represent a continuum with overlapping features in neurodegenerative diseases, but differences in protein components and affected brain regions(1). The molecular hallmark of synucleinopathies such as Parkinson's disease, dement ...

Nature Publishing Group2015

Detection of Alzheimer’s disease amyloid-beta plaque deposition by deep brain impedance profiling

Philippe Renaud, Patrick Fraering, Amélie Barbara Hildegarde Béduer, Pierre Joris, Sébastien Mosser

OBJECTIVE: Alzheimer disease (AD) is the most common form of neurodegenerative disease in elderly people. Toxic brain amyloid-beta (ASS) aggregates and ensuing cell death are believed to play a central role in the pathogenesis of the disease. In this study ...

Iop Publishing Ltd2015

Trans‐seeding of Alzheimer‐related tau protein by a yeast prion

Henning Paul-Julius Stahlberg

Abnormal tau protein aggregates constitute a hallmark of Alzheimer's disease. The mechanisms underlying the initiation of tau aggregation in sporadic neurodegeneration remain unclear. Here we investigate whether a non-human prion can seed tau aggregation. ...

2022

Clinical Proton MR Spectroscopy in Central Nervous System Disorders

Rolf Gruetter, Cristina Ramona Cudalbu Moldovan

A large body of published work shows that proton (hydrogen 1 [(1)H]) magnetic resonance (MR) spectroscopy has evolved from a research tool into a clinical neuroimaging modality. Herein, the authors present a summary of brain disorders in which MR spectrosc ...

2014

Tau seeds from patients induce progressive supranuclear palsy pathology and symptoms in primates

Grégoire Courtine, Tomislav Milekovic, Flavio Raschella

Progressive supranuclear palsy is a primary tauopathy affecting both neurons and glia and is responsible for both motor and cognitive symptoms. Recently, it has been suggested that progressive supranuclear palsy tauopathy may spread in the brain from cell ...

OXFORD UNIV PRESS2022

Two Misfolding Routes for the Prion Protein around pH 4.5

Ursula Röthlisberger, Ivano Tavernelli

Using molecular dynamics simulations, we show that the prion protein (PrP) exhibits a dual behavior, with two possible transition routes, upon protonation of H187 around pH 4.5, which mimics specific conditions encountered in endosomes. Our results suggest ...

Public Library Science2013

Hyperpolarized (1-13C)Alaninamide Is a Multifunctional In Vivo Sensor of Aminopeptidase N Activity, pH, and CO2

Rolf Gruetter, Hikari Ananda Infinity Yoshihara, Daniel Ortiz Trujillo, Alice Radaelli

Spin hyperpolarization enables real-time metabolic imaging of carbon-13-labeled substrates. While hyperpolarized L- (1-13C)alaninamide is a probe of the cell-surface tumor marker aminopeptidase-N (APN, CD13), its activity in vivo has not been described. Sc ...

AMER CHEMICAL SOC2022

Prion versus Doppel Protein Misfolding: New Insights from Replica-Exchange Molecular Dynamics Simulations

Ursula Röthlisberger, Ivano Tavernelli

The doppel (Dpl) and prion (PrP) proteins share a very similar fold (three helices and two short beta-strands), while they differ significantly in sequence (only 25% homologous) and in disease-related beta-rich conformations that occur for PrP only. In a p ...

American Chemical Society2013

Abnormal brain oxygen homeostasis in an animal model of liver disease

Cristina Ramona Cudalbu Moldovan, Dunja Simicic, Katarzyna Pierzchala

Background & Aims: Increased plasma ammonia concentration and consequent disruption of brain energy metabolism could underpin the pathogenesis of hepatic encephalopathy (HE). Brain energy homeostasis relies on effective maintenance of brain oxygenation, an ...

ELSEVIER2022

Transgenic expression of beta 1 antibody in brain neurons impairs age-dependent amyloid deposition in APP23 mice

Maurizio Molinari

Heterologous expression of the functional amyloid beta (A beta) antibody beta 1 in the central nervous system was engineered to maximize antibody exposure in the brain and assess the effects on A beta production and accumulation in these conditions. A sing ...

Elsevier Science Inc2013

Metabolic and transcriptomic profiles of glioblastoma invasion revealed by comparisons between patients and corresponding orthotopic xenografts in mice

Cristina Ramona Cudalbu Moldovan, Lijing Xin, Mario Gaetano Lepore, Marta Lai

The invasive behavior of glioblastoma, the most aggressive primary brain tumor, is considered highly relevant for tumor recurrence. However, the invasion zone is difficult to visualize by Magnetic Resonance Imaging (MRI) and is protected by the blood brain ...

2021

Improved Prediction of Carbonless NMR Spectra by the Machine Learning of Theoretical and Fragment Descriptors for Environmental Mixture Analysis

Xiangru Xu

As the first multidimensional NMR approach, 2D J-resolved (2DJ) spectroscopy is distinguished by signal resolution and detection sensitivity with remarkable advantages for the exhaustive evaluation of complex mixtures and environmental samples due to its c ...

2021

In Vivo Magnetic Resonance Spectroscopy (MRS) of the Activated Human Brain at 7T

Benoît Schaller

The principal aim of this thesis was to investigate human brain energy metabolism during physiological activation using proton (1H) magnetic resonance spectroscopy (MRS) at 7 Tesla (T). High magnetic fields (≥ 7 T) provide several advantages in human brain ...

EPFL2013

To target Tau pathologies, we must embrace and reconstruct their complexities

Hilal Lashuel, Galina Limorenko

The accumulation of hyperphosphorylated fibrillar Tau aggregates in the brain is one of the defining hallmarks of Tauopathy diseases, including Alzheimer's disease. However, the primary events or molecules responsible for initiation of the pathological Tau ...

ACADEMIC PRESS INC ELSEVIER SCIENCE2021

Enhanced Sampling Molecular Dynamics Identifies PrPSc Structures Harboring a C-Terminal beta-Core

Ursula Röthlisberger, Ivano Tavernelli, Maria Carola Colombo

We perform a replica exchange molecular dynamics simulation corresponding to a 2.8 mu s total time for the extensive enhanced sampling of the conformational space of the C-terminal part (residues 124-226) of the mouse prion protein (PrP); 1.3% of the confo ...

Amer Chemical Soc2012

Radical-free hyperpolarized MRI using endogenously occurring pyruvate analogues and UV-induced nonpersistent radicals

Rolf Gruetter, Josefina Adriana Maria Bastiaansen, Hikari Ananda Infinity Yoshihara, Andrea Capozzi, Alice Radaelli, Claudia Christina Zanella

It was recently demonstrated that nonpersistent radicals can be generated in frozen solutions of metabolites such as pyruvate by irradiation with UV light, enabling radical-free dissolution dynamic nuclear polarization. Although pyruvate is endogenous, the ...

WILEY2021