Publication
Structural and Functional Determinants of gamma-Secretase, an Intramembrane Protease Implicated in Alzheimer's Disease
Related publications (38)
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 ...
SPRINGER2019Zinc 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 Inc2017Human Kunitz-type protease inhibitor engineered for enhanced matrix retention extends longevity of fibrin biomaterials
Peter Frey, Jeffrey Alan Hubbell, Hans Mattias Larsson, Priscilla Suhasna Maithili Briquez, Kristen Lorentz
Aprotinin is a broad-spectrum serine protease inhibitor used in the clinic as an anti-fibrinolytic agent in fibrin-based tissue sealants. However, upon re-exposure, some patients suffer from hypersensitivity immune reactions likely related to the bovine or ...
2017The 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 Ltd2016Endogenous Regulators of Gamma-Secretase and Amyloid-Beta Production, and Engineering of Alzheimer's Disease Therapeutic Tools
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 ...
EPFL2016Production 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-Blackwell2015The 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 Press2015Identification 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-Blackwell2015The 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 Group2015Perturbations 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