Publication

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

Publications associées (34)

Real-time Protein Aggregation Monitoring with a Bloch Surface Wavebased Approach

Hans Peter Herzig, Elsie Barakat, Sara Santi

The misfolding and aggregation of amyloid proteins has been associated with incurable diseases such as Alzheimer's or Parkinson's disease. In the specific case of Alzheimer's disease, recent studies have shown that cell toxicity is caused by soluble oligom ...

Spie-Int Soc Optical Engineering2014

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

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

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

Valérie Eligert, 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

Gamma-Secretase Dependent Gene Expression

Alexandra Marie-Isabelle Karoline Brigitte Magold

The causes of sporadic Alzheimer's Disease (AD), the most common form of dementia at old age, are still unknown. Familial early onset AD (FAD) is mainly caused by mutations of Presenilins (PS), the active subunits of γ-secretase. Processing of its substrat ...

EPFL2011

The Gamma-Secretase-Mediated Proteolytic Processing of APP C-Terminal Fragments as a Therapeutic Target for Alzheimer's Disease

Jemila Houacine

Alzheimer's disease (AD) is a devastating neurodegenerative disorder which severely impairs cognitive functions by triggering neuronal cell death and synaptic loss, and finally leads the patients to death. Two main histopathological hallmarks can be found ...

EPFL2011

Nucleation Dependent Polymerization of Amyloid-ß (Aß) as an Important Determinant of Aß Amyloid Formation and Neurotoxicity

Mohammad Asad Jan Qureshi

Aggregation and fibril formation of amyloid-β (Aβ) peptides play a pivotal role in the pathogenesis of Alzheimer's disease (AD). Aβ peptides, principally comprising of 40 or 42 amino acid residues (Aβ40 and Aβ42), are produced by proteolytic processing of ...

EPFL2010

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

Lorène Aeschbach, Patrick Fraering, 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

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

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

Lorène Aeschbach, Patrick Fraering, 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

Amyloid ß-derived switch-peptides as tool to study conformational changes relevant in degenerative diseases

Marie-Stéphanie Camus

The rapid growing number of patients diagnosed with a neurodegenerative disease and more particularly with Alzheimer's disease (AD) has stimulated intensive research in determining and understanding biological phenomena causing such devastating diseases an ...

EPFL2008

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