Publications related to Gamma secretase

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

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

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

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, Virginie Sandra Braman, Patrick Fraering, Mitko Dimitrov, Hermeto Gerber, Andres Ricardo Lopez Robles

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

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

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, Alexandre Matz

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

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

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

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

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

Seamless Integration of Dose-Response Screening and Flow Chemistry: Efficient Generation of Structure-Activity Relationship Data of β-Secretase (BACE1) Inhibitors

Horst Vogel, Michael Werner

Drug discovery is a multifaceted endeavor encompassing as its core element the generation of structure-activity relationship (SAR) data by repeated chemical synthesis and biological testing of tailored molecules. Herein, we report on the development of a f ...

Wiley-Blackwell2014

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Gamma secretase

Proteolytic processing of the synaptic cell adhesion molecule neurexin-3beta and the neurobiological functions of the resulting cleavage products

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

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

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

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

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

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

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

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

Seamless Integration of Dose-Response Screening and Flow Chemistry: Efficient Generation of Structure-Activity Relationship Data of β-Secretase (BACE1) Inhibitors

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

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

Seamless Integration of Dose-Response Screening and Flow Chemistry: Efficient Generation of Structure-Activity Relationship Data of β-Secretase (BACE1) Inhibitors

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

Proteolytic processing of the synaptic cell adhesion molecule neurexin-3beta and the neurobiological functions of the resulting cleavage products

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

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

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

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

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