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Patrick Fraering

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Related publications (41)

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Shedding of neurexin 3 beta ectodomain by ADAM10 releases a soluble fragment that affects the development of newborn neurons

Patrick Fraering, Mitko Dimitrov, Magda Maria Palczynska

Neurexins are transmembrane synaptic cell adhesion molecules involved in the development and maturation of neuronal synapses. In the present study, we report that Nrxn3 beta is processed by the metalloproteases ADAM10, ADAM17, and by the intramembrane-clea ...

Nature Research2016

NOVEL MECHANISM-BASED INHIBITORS OF A beta AGGREGATION AND TOXICITY

Hilal Lashuel, Patrick Fraering

Elsevier Science Inc2014

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

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

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 mutations in APP but not γ-secretase modulators affect epsilon-cleavage-dependent AICD production

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

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

Structural and Functional Determinants of gamma-Secretase, an Intramembrane Protease Implicated in Alzheimer's Disease

Patrick Fraering

Alzheimer's disease is the most common form of neurodegenerative diseases in humans, characterized by the progressive accumulation and aggregation of amyloid-beta peptides (Abeta) in brain regions subserving memory and cognition. These 39-43 amino acids lo ...

Bentham Science Publishers2007

The adipocyte differentiation protein APMAP is an endogenous suppressor of Aβ production in the brain

Bernard Schneider, Patrick Fraering, Mitko Dimitrov, Sébastien Mosser, Justine Pascual

The deposition of amyloid-beta (Aβ) aggregates in the brain is a major pathological hallmark of Alzheimer's disease (AD). Aβ is generated from the cleavage of C-terminal fragments of the amyloid precursor protein (APP-CTFs) by γ-secretase, an intramembrane ...

Oxford University Press2015

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

Patrick Fraering, Lorène Aeschbach

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

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

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

Accurate resistivity mouse brain mapping using microelectrode arrays

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

Electrical impedance spectroscopy measurements were performed in post-mortem mice brains using a flexible probe with an embedded micrometric electrode array. Combined with a peak resistance frequency method this allowed obtaining intrinsic resistivity valu ...

Elsevier2014

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

A Simple and Reliable PDMS and SU-8 Irreversible Bonding Method and Its Application on a Microfluidic-MEA Device for Neuroscience Research

Philippe Renaud, Arnaud Bertsch, Patrick Fraering, Marc Olivier Heuschkel, Sébastien Mosser, Yufei Ren

Polydimethylsiloxane (PDMS) and SU-8 are currently two very commonly used polymeric materials in the microfluidics field for biological applications. However; there is a pressing need to find a simple, reliable, irreversible bonding method between these tw ...

MDPI2015

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

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

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

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

Cell Press2014

Therapeutic antibodies targeting app-c99

Lorène Aeschbach, Patrick Fraering, Tristan Bolmont, Jemila Houacine

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

The lipidome associated with the gamma-secretase complex is required for its integrity and activity

Henning Paul-Julius Stahlberg, Patrick Fraering, Hermeto Gerber

gamma-Secretase is a multi-subunit membrane protease complex that catalyses the final intramembrane cleavage of the beta-amyloid precursor protein (APP) during the neuronal production of amyloid-beta peptides (A beta), which are implicated as the causative ...

Portland Press Ltd2016

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

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

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

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

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

Cell Press2013

Substrate-targeting gamma-secretase modulators

Patrick Fraering

Selective lowering of Abeta42 levels (the 42-residue isoform of the amyloid-beta peptide) with small-molecule gamma-secretase modulators (GSMs), such as some non-steroidal anti-inflammatory drugs, is a promising therapeutic approach for Alzheimer's disease ...

Nature Publishing Group2008

Mimicking Alzheimer's disease spreading via an integrated microfluidics-MEA device in vitro

Philippe Renaud, Patrick Fraering, Sébastien Mosser, Marc Olivier Heuschkel, Yufei Ren

2015