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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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 ...

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 ...

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 ...

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 ...

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 ...

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 ...

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. ...

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 ...

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 ...

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 ...

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 ...

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 ...

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 ...

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 ...

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 ...

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 ...

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 ...

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 ...

In the context of an ageing society neurodegenerative disease have become more and more frequent among humans. Opposing the benefits of a longer life, these diseases have thus triggered research on neurons and how they interact with each other. In vitro as ...

Hippocampus plays a critical role in linking brain energetics and behavior typically associated to stress exposure. In this study, we aimed to simultaneously assess excitatory and inhibitory neuronal metabolism in mouse hippocampus in vivo by applying (18) ...

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

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

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

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

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

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

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

Clinical Proton MR Spectroscopy in Central Nervous System Disorders

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

Two Misfolding Routes for the Prion Protein around pH 4.5

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

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

Abnormal brain oxygen homeostasis in an animal model of liver disease

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

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

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

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

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

Characterisation of Living Matter Using Advanced Spectroscopy Techniques

Excitatory/inhibitory neuronal metabolic balance in mouse hippocampus upon infusion of [U-C-13(6)]glucose