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

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Publications associées (32)

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

Endogenous Regulators of Gamma-Secretase and Amyloid-Beta Production, and Engineering of Alzheimer's Disease Therapeutic Tools

Sébastien Mosser

Alzheimer s disease (AD) is a devastating neurodegenerative disease characterized by strong cognitive impairment and memory loss. These symptoms are caused by neuronal death, induced by two pathological hallmarks: extracellular senile plaques composed of a ...

EPFL2016

Effect of the Synaptic Plasma Membrane on the Stability of the Amyloid Precursor Protein Homodimer

Thomas Lemmin, Matteo Dal Peraro, Alessandro Barducci, Martina Audagnotto

The proteolytic cleavage of the transmembrane (TM) domain of the amyloid precursor protein (APP) releases amyloid-beta (A beta) peptides, which accumulation in the brain tissue is an early indicator of Alzheimer's disease. We used multiscale molecular dyna ...

Amer Chemical Soc2016

A subcutaneous cellular implant for passive immunization against amyloid-beta reduces brain amyloid and tau pathologies

Patrick Aebischer, Bernard Schneider, Vanessa Laversenne, Aurélien Lathuilière, Marco Stampanoni

Passive immunization against toxic misfolded proteins could offer protection against neurodegenerative disease. LathuiliSre et al. report the development of a retrievable device to encapsulate cells secreting recombinant anti-amyloid-beta antibodies. When ...

Oxford Univ Press2016

Structure of Crenezumab Complex with A beta Shows Loss of beta-Hairpin

Andrea Pfeifer, Andreas Muhs, Bing Li

Accumulation of amyloid-beta (A beta) peptides and amyloid plaque deposition in brain is postulated as a cause of Alzheimer's disease (AD). The precise pathological species of A beta remains elusive although evidence suggests soluble oligomers may be prima ...

Nature Research2016

Amyloid-beta oligomerization is associated with the generation of a typical peptide fragment fingerprint

Cyntia De Piano, Nikita Rudinskiy, Adrian Schmid, Marc Moniatte, Davide Demurtas, Christophe Fuerer

Amyloid-beta (A beta) peptide oligomerization plays a central role in the pathogenesis of Alzheimer's disease (AD), and A beta oligomers are collectively considered an appealing therapeutic target for the treatment of AD. However, the molecular mechanisms ...

Elsevier Science Inc2016

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

Structural differences of amyloid-beta fibrils revealed by antibodies from phage display

Hilal Lashuel, Patrick Droste

Background: Beside neurofibrillary tangles, amyloid plaques are the major histological hallmarks of Alzheimer's disease (AD) being composed of aggregated fibrils of beta-amyloid (A beta). During the underlying fibrillogenic pathway, starting from a surplus ...

Biomed Central Ltd2015

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

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

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

New Insights Into Amyloid Formation and Structure by Innovative Atomic Force Microscopy Methods

Francesco Simone Ruggeri

Today, more than 40 million people worldwide are affected by neurodegenerative disorders. Onset of these diseases is associated with insoluble fibrillar protein aggregates, termed amyloids. The molecular origin and the link between amyloid formation and di ...

EPFL2015

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