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Patrick Fraering

Cette personne n’est plus à l’EPFL

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Publications associées (42)

Inactivation of brain Cofilin-1 by age, Alzheimer's disease and gamma-secretase

Patrick Fraering, Sébastien Mosser, Eugenio Barone

Rapid remodeling of the actin cytoskeleton in the pre- and/or post-synaptic compartments is responsible for the regulation of neuronal plasticity, which is an important process for learning and memory. Cofilin1 plays an essential role in these processes an ...

Elsevier Science Bv2014

The Amyloid Precursor Protein Maintains an Ideal&Alpha-Helical Conformation in the Lipid Bilayer

Thomas Lemmin, Patrick Fraering, Matteo Dal Peraro, Mitko Dimitrov

Cell Press2014

Highly efficient production of the Alzheimer's γ-Secretase integral membrane protease complex by a multi-gene stable integration approach

Florian Maria Wurm, David Hacker, Patrick Fraering, Lorène Aeschbach, Mitko Dimitrov, Sowmya Balasubramanian

Inefficient production of membrane-embedded multi-protein complexes by conventional methods has largely prevented the generation of high-resolution structural information and the performance of high-throughput drug discovery screens for this class of prote ...

2013

Alzheimer's disease mutations in APP but not γ-secretase modulators affect epsilon-cleavage-dependent AICD production

Thomas Lemmin, Patrick Fraering, Freddy Radtke, Rajwinder Lehal, Jemila Houacine, Matteo Dal Peraro, Mitko Dimitrov, Andrzej Jacek Fligier

Pathological amino-acid substitutions in the amyloid precursor protein (APP) and chemical gamma-secretase modulators affect the processing of APP by the gamma-secretase complex and the production of the amyloid-beta peptide A beta 42, the accumulation of w ...

Nature Publishing Group2013

Use of waste products for detecting amyloidogenic proteinaceous material in living mammals

Theo Lasser, Patrick Fraering, Tristan Bolmont, Taoufiq Harach

Method for detecting amyloidogenic proteinaceous material induced by a proteopathy, for instance Alzheimer's disease, characterized by the fact that said amyloidogenic proteinaceous material is detected in a mammal waste product, such as feces. ...

2013

The Role of γ-Secretase Activating Protein (GSAP) and Imatinib in the Regulation of γ-Secretase Activity and Amyloid-β Generation

Patrick Fraering, Mitko Dimitrov, Valérie Eligert

gamma-Secretase is a large enzyme complex comprising presenilin, nicastrin, presenilin enhancer 2, and anterior pharynx-defective 1 that mediates the intramembrane proteolysis of a large number of proteins including amyloid precursor protein and Notch. Rec ...

2013

Intrinsic Transmembrane Flexibility of the Amyloid Precursor Protein Explored by Molecular Simulations

Thomas Lemmin, Patrick Fraering, Matteo Dal Peraro, Mitko Dimitrov

Cell Press2013

Therapeutic antibodies targeting app-c99

Patrick Fraering, Lorène Aeschbach, Jemila Houacine, Tristan Bolmont

The present invention relates to an isolated and/or purified antibody, antibody fragment or derivative thereof able to block the gamma-secretase-dependent processing of the amyloid precursor protein (APP) and to pharmaceutical compositions containing said ...

2012

Selective neutralization of APP-C99 with monoclonal antibodies reduces the production of Alzheimer's Aβ peptides

Patrick Fraering, Lorène Aeschbach, Jemila Houacine, Tristan Bolmont

The toxic amyloid-β (Aβ) peptides involved in Alzheimer's disease (AD) are produced after processing of the amyloid precursor protein-C-terminal fragment APP-C99 by γ-secretase. Thus, major therapeutic efforts have been focused on inhibiting the activity o ...

Elsevier Science Inc2012

Generation of monoclonal antibody fragments binding the native γ-secretase complex for use in structural studies

Patrick Fraering, Lorène Aeschbach, Claude André Schweizer, Mitko Dimitrov

A detailed understanding of γ-secretase structure is crucially needed to elucidate its unique properties of intramembrane protein cleavage and to design therapeutic compounds for the safe treatment of Alzheimer's disease. γ-Secretase is an enzyme complex c ...

Amer Chemical Soc2012

Alzheimer's Disease-Linked Mutations in Presenilin-1 Result in a Drastic Loss of Activity in Purified gamma-Secretase Complexes

Patrick Fraering, Lorène Aeschbach, Jemila Houacine

Background: Mutations linked to early onset, familial forms of Alzheimer's disease (FAD) are found most frequently in PSEN1, the gene encoding presenilin-1 (PS1). Together with nicastrin (NCT), anterior pharynx-defective protein 1 (APH1), and presenilin en ...

Public Library of Science2012

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

Theo Lasser, Martin Villiger, Corinne Berclaz, Christophe Pache, Patrick Fraering, Tristan Bolmont, Mitko Dimitrov, Arno Pino Bouwens

We demonstrate label-free imaging of cerebral β-amyloidosis ex vivo and in a living mouse model of Alzheimer's disease using extended focus Fourier domain optical coherence microscopy (xfOCM). xfOCM provides 3D, high-resolution images of individual β-amylo ...

Society for Neuroscience2012

Discovery of a novel pharmacological and structural class of gamma secretase modulators derived from the extract of Actaea racemosa

Patrick Fraering

A screen of a library of synthetic drugs and natural product extracts identified a botanical extract that modulates the processing of amyloid precursor protein (APP) in cultured cells to produce a lowered ratio of amyloid-beta peptide (1-42) (Aβ42) relativ ...

2012

Gamma-Secretase activity alterations affect Wnt pathway gene transcription in CHO cells

Patrick Fraering, Alexandra Marie-Isabelle Karoline Brigitte Magold

Elsevier2011

Mercury is a direct and potent γ-secretase inhibitor affecting Notch processing and development in Drosophila

Patrick Fraering, Bruno Lemaitre, Mitko Dimitrov, Takayuki Kuraishi, Isabelle Chang

Prenatal exposure to mercury causes neurodevelopmental disorders and neurological pathologies in infants, such as microcephaly and mental retardation. Despite critical importance, the molecular interactions leading to mercury toxicity are yet to be elucida ...

2011

Novel gamma-secretase inhibitors uncover a common nucleotide-binding site in JAK3, SIRT2, and PS1

Nikita Rudinskiy, Patrick Fraering, Claude André Schweizer

Gamma-secretase is an intramembrane-cleaving protease responsible for the final proteolytic event in the production of the amyloid-beta peptides (Abeta) implicated in Alzheimer's disease (AD). Inhibition of gamma-secretase activity is thus an attractive th ...

2010

Processing of the synaptic cell adhesion molecule neurexin-3beta by Alzheimer disease alpha- and gamma-secretases

Patrick Fraering, Saoussen Ben Halima, Claude André Schweizer, Nathalie Bot

Neurexins (NRXNs) are synaptic cell adhesion molecules having essential roles in the assembly and maturation of synapses into fully functional units. Immunocytochemical and electrophysiological studies have shown that specific binding across the synaptic c ...

American Society for Biochemistry and Molecular Biology2010

Gene expression profiling in cells with enhanced gamma-secretase activity

Patrick Fraering, Alexandra Marie-Isabelle Karoline Brigitte Magold

BACKGROUND: Processing by gamma-secretase of many type-I membrane protein substrates triggers signaling cascades by releasing intracellular domains (ICDs) that, following nuclear translocation, modulate the transcription of different genes regulating a div ...

Public Library of Science2009

Cryoelectron microscopy structure of purified gamma-secretase at 12 A resolution

Patrick Fraering, Lorène Aeschbach, Hua Li

Gamma-secretase, an integral membrane protein complex, catalyzes the intramembrane cleavage of the beta-amyloid precursor protein (APP) during the neuronal production of the amyloid beta-peptide. As such, the protease has emerged as a key target for develo ...

Elsevier2009

Rapid purification of active gamma-secretase, an intramembrane protease implicated in Alzheimer's disease

Patrick Fraering, Lorène Aeschbach, Hua Li

Gamma-secretase is an unconventional aspartyl protease that processes many type 1 membrane proteins within the lipid bilayer. Because its cleavage of amyloid-beta precursor protein generates the amyloid-beta protein (Abeta) of Alzheimer's disease, partiall ...

Wiley-Blackwell2008

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