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Label-free imaging of cerebral β-amyloidosis with extended-focus optical coherence microscopy

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The metalloprotease ADAMTS4 generates N-truncated A4-x species and marks oligodendrocytes as a source of amyloidogenic peptides in Alzheimer's disease

Patrick Fraering, Mitko Dimitrov, Hermeto Gerber

Brain accumulation and aggregation of amyloid- (A) peptides is a critical step in the pathogenesis of Alzheimer's disease (AD). Full-length A peptides (mainly A1-40 and A1-42) are produced through sequential proteolytic cleavage of the amyloid precursor pr ...

SPRINGER2019

Membrane–Protein–Hydration Interaction of α-Synuclein with Anionic Vesicles Probed via Angle-Resolved Second-Harmonic Scattering

Sylvie Roke, Jan Dedic, Halil Ibrahim Okur

Amyloid formation of the protein α-synuclein promotes neurodegeneration in Parkinson's disease. The normal function of α-synuclein includes synaptic vesicle transport and fusion, and the protein binds strongly to negatively charged vesicles in vitro. Here, ...

2019

Parameter-free image resolution estimation based on decorrelation analysis

Aleksandra Radenovic, Adrien Charles-François Raymond Descloux, Kristin Stefanie Grussmayer

Super-resolution microscopy opened diverse new avenues of research by overcoming the resolution limit imposed by diffraction. Exploitation of the fluorescent emission of individual fluorophores made it possible to reveal structures beyond the diffraction l ...

Nature Publishing Group2019

Optical projection tomography for whole organ imaging

David Nguyen

In the past twenty years, far-reaching studies of molecular and cellular processes have reached a milestone in their maturation, and the knowledge from these studies was ready to apply at higher organizational levels. At that time, rodent models were long ...

EPFL2019

A viral vector based in vivo model of tauopathy to explore therapeutic strategies against tau pathology

Sameer Mohammad Khaleel Nazeeruddin

Tauopathies are neurodegenerative diseases whose common pathological feature is the intraneuronal accumulation of tau aggregates. Tau protein has various roles in the neuron, among which stabilization of microtubules (MT), regulation of synaptic activity o ...

EPFL2019

The virtuous cycle of human genetics and mouse models in drug discovery

Johan Auwerx

Ongoing studies in many species seek to understand the origins, architecture and consequences of phenotypic variation under normal and dysfunctional conditions, with the aim of identifying targets for intervention that can prevent, stabilize or reverse dis ...

NATURE PUBLISHING GROUP2019

Crosslinking Allosteric Sites on the Nucleosome Core Particle

Lucinda Kate Batchelor

Designing compounds that bind to the acidic patch of the nucleosome core particle (NCP) is an emerging therapeutic approach that can inhibit the binding of key chromatin factors. Pretreatment of human ovarian carcinoma, A2780, cells with RAPTA-T, an antime ...

EPFL2019

Calorie restriction slows age-related microbiota changes in an Alzheimer's disease model in female mice

Julia Chiara Vincentini

Alzheimer's disease (AD) affects an estimated 5.8 million Americans, and advanced age is the greatest risk factor. AD patients have altered intestinal microbiota. Accordingly, depleting intestinal microbiota in AD animal models reduces amyloid-beta (A beta ...

Springer Nature2019

Methods of treating amyloid-beta peptide diseases

Johan Auwerx, Laurent Mouchiroud, Vincenzo Sorrentino

The present invention is directed to a method of treating an amyloid-3 peptide disease in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound that enhances mitochondrial proteostasi ...

2018

Enhancing mitochondrial proteostasis reduces amyloid-beta proteotoxicity

Johan Auwerx, Adrian Schmid, Norman Lionel Moullan, Hongbo Zhang, Vincenzo Sorrentino, Davide D'Amico, Mario Romani

Alzheimer's disease is a common and devastating disease characterized by aggregation of the amyloid-beta peptide. However, we know relatively little about the underlying molecular mechanisms or how to treat patients with Alzheimer's disease. Here we provid ...

2017

Association of brain amyloidosis with pro-inflammatory gut bacterial taxa and peripheral inflammation markers in cognitively impaired elderly

Tristan Bolmont, Taoufiq Harach

The pathway leading from amyloid-b deposition to cognitive impairment is believed to be a cornerstone of the pathogenesis of Alzheimer's disease (AD). However, what drives amyloid buildup in sporadic nongenetic cases of AD is still unknown. AD brains featu ...

Elsevier Science Inc2017

Administrations of human adult ischemia-tolerant mesenchymal stem cells and factors reduce amyloid beta pathology in a mouse model of Alzheimer's disease

Theo Lasser, Tristan Bolmont, Taoufiq Harach, Fabien Louis Claude Robert Jammes

The impact of human adult ischemia-tolerant mesenchymal stem cells (hMSCs) and factors (stem cell factors) on cerebral amyloid beta (Aβ) pathology was investigated in a mouse model of Alzheimer's disease (AD). To this end, hMSCs were administered intraveno ...

Elsevier2017

Amyloid Single Cell Cytotoxicity Assays by Nanomotion Detection

Giovanni Dietler, Hilal Lashuel, Sandor Kasas, Giovanni Longo, Francesco Simone Ruggeri, Anne-Laure Mahul Mellier

Cells are extremely complex systems able to modify actively their metabolism and behaviour in response to environmental conditions and stimuli, such as pathogenic agents or drugs. The comprehension of these responses is central to understand the molecular ...

Springer Nature2017