Publications by Patrick Fraering

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, Sandra Lehmann

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

Zinc and Copper Differentially Modulate Amyloid Precursor Protein Processing by -Secretase and Amyloid- Peptide Production

Patrick Fraering, Mitko Dimitrov, Hermeto Gerber, Guillermo Miguel Garcia Osuna

Recent evidence suggests involvement of biometal homeostasis in the pathological mechanisms in Alzheimer's disease (AD). For example, increased intracellular copper or zinc has been linked to a reduction in secreted levels of the AD-causing amyloid- peptid ...

Amer Soc Biochemistry Molecular Biology Inc2017

Regulated intramembrane proteolysis of the AXL receptor kinase generates an intracellular domain that localizes in the nucleus of cancer cells

Patrick Fraering

Deregulation of the TAM (TYRO3, AXL, and MERTK) family of receptor tyrosine kinases (RTKs) has recently been demonstrated to predominately promote survival and chemoresistance of cancer cells. Intramembrane proteolysis mediated by presenilin/gamma-secretas ...

Federation Amer Soc Exp Biol2017

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

Henning Paul-Julius Stahlberg, Patrick Fraering, Hermeto Gerber, Guillermo Miguel Garcia Osuna

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

Inhibition of Notch pathway arrests PTEN-deficient advanced prostate cancer by triggering p27-driven cellular senescence

Patrick Fraering, Mitko Dimitrov, Hermeto Gerber, Maria Luna Perciato, Jingjing Chen, Andrea Rinaldi

Activation of NOTCH signalling is associated with advanced prostate cancer and treatment resistance in prostate cancer patients. However, the mechanism that drives NOTCH activation in prostate cancer remains still elusive. Moreover, preclinical evidence of ...

Nature Publishing Group2016

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

Patrick Fraering, Erika Myrna Borcel Novoa, Giorgio Ulrich, Mitko Dimitrov, Magda Maria Palczynska, Marine Krzisch

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

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

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

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

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

Marc Olivier Heuschkel, Philippe Renaud, Arnaud Bertsch, Patrick Fraering, Yufei Ren, Sébastien Mosser, Shun-Ho Huang, Jingjing Chen

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

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

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

2015

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

Bernard Schneider, Patrick Fraering, Alexandre Matz, 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

The FDA-approved natural product dihydroergocristine reduces the production of the Alzheimer's disease amyloid-beta peptides

Patrick Fraering, Jianhua Liu, Jing Yu

Known gamma-secretase inhibitors or modulators display an undesirable pharmacokinetic profile and toxicity and have therefore not been successful in clinical trials for Alzheimer's disease (AD). So far, no compounds from natural products have been identifi ...

Nature Publishing Group2015

A Compressible Scaffold for Minimally Invasive Delivery of Large Intact Neuronal Networks

Philippe Renaud, Thomas Michael Braschler, Patrick Fraering, Oliver Peric, Georg Fantner, Sébastien Mosser, Amélie Barbara Hildegarde Béduer, Sidi Ahmed Bencherif

Millimeter to centimeter-sized injectable neural scaffolds based on macroporous cryogels are presented. The polymer-scaffolds are made from alginate and carboxymethyl-cellulose by a novel simple one-pot cryosynthesis. They allow surgical sterility by means ...

Wiley-VCH Verlag2015

Identification of new Presenilin-1 phosphosites: implication for gamma-secretase activity and A beta production

Marc Moniatte, Patrick Fraering, Blanka Halamoda, Alexandre Matz, Mitko Dimitrov, Romain Hamelin, Sébastien Mosser

An important pathological hallmark of Alzheimer's disease (AD) is the deposition of amyloid-beta (A) peptides in the brain parenchyma, leading to neuronal death and impaired learning and memory. The protease -secretase is responsible for the intramembrane ...

Wiley-Blackwell2015

Production of active glycosylation-deficient gamma-secretase complex for crystallization studies

Florian Maria Wurm, David Hacker, Patrick Fraering, Mitko Dimitrov, Andres Ricardo Lopez Robles, Hermeto Gerber, Virginie Sandra Braman

Alzheimer's disease (AD)-associated gamma-secretase is a ubiquitously expressed multi-subunit protease complex embedded in the lipid bilayer of cellular compartments including endosomes and the plasma membrane. Although gamma-secretase is of crucial intere ...

Wiley-Blackwell2015

Perturbations of the Straight Transmembrane alpha-Helical Structure of the Amyloid Precursor Protein Affect Its Processing by gamma-Secretase

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

Background: Amyloid- neurotoxicity depends on the specificity of the proteolytic cleavage of the amyloid precursor protein (APP) transmembrane domain. Results: The APP transmembrane -helix is straight in a biological membrane bilayer. Conclusion: The flexi ...

American Society for Biochemistry and Molecular Biology2014

NOVEL MECHANISM-BASED INHIBITORS OF A beta AGGREGATION AND TOXICITY

Hilal Lashuel, Patrick Fraering, Saviana Di Giovanni, Simona Eleuteri

Elsevier Science Inc2014

Accurate resistivity mouse brain mapping using microelectrode arrays

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

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

Anti-nicastrin monoclonal antibodies elicit pleiotropic anti-tumour pharmacological effects in invasive breast cancer cells (vol 148, pg 455, 2014)

Patrick Fraering

Springer2014

Ferritin H gene deletion in the choroid plexus and forebrain results in hydrocephalus

Patrick Fraering, Claude André Schweizer

Ferritin H, the major iron storage protein, has essential functions in early embryonic development as well as in adult liver and intestine. To address the question whether ferritin H has similarly essential functions in the brain we used the Cre/loxP syste ...

Elsevier2014

Anti-nicastrin monoclonal antibodies elicit pleiotropic anti-tumour pharmacological effects in invasive breast cancer cells

Patrick Fraering

The goal of targeted cancer therapies is to specifically block oncogenic signalling, thus maximising efficacy, while reducing side-effects to patients. The gamma-secretase (GS) complex is an attractive therapeutic target in haematological malignancies and ...

Springer2014