Publications de Lorène Aeschbach

Comparative Analysis of Total Alpha-Synuclein (alpha SYN) Immunoassays Reveals That They Do Not Capture the Diversity of Modified alpha SYN Proteoforms

Hilal Lashuel, Lorène Aeschbach, Mohamed Bilal Fares, Ritwik Burai, Layane Hanna-el-Daher, Lara Petricca

Background: The development of therapeutics for Parkinson's disease (PD) requires the establishment of biomarker assays to enable stratifying patients, monitoring disease progression, and assessing target engagement. Attempts to develop diagnostic assays b ...

IOS PRESS2022

N-terminal mutant huntingtin deposition correlates with CAG repeat length and symptom onset, but not neuronal loss in Huntington's disease

Hilal Lashuel, Lorène Aeschbach, Nathan Alain Denis Riguet

Huntington's disease (HD) is caused by a CAG repeat expansion mutation in the gene encoding the huntingtin (Htt) protein, with mutant Htt protein subsequently forming aggregates within the brain. Mutant Htt is a current target for novel therapeutic strateg ...

ACADEMIC PRESS INC ELSEVIER SCIENCE2022

Highly efficient production of the Alzheimer's γ-Secretase integral membrane protease complex by a multi-gene stable integration approach

Florian Maria Wurm, David Hacker, Patrick Fraering, Lorène Aeschbach, Mitko Dimitrov, Sowmya Balasubramanian

Inefficient production of membrane-embedded multi-protein complexes by conventional methods has largely prevented the generation of high-resolution structural information and the performance of high-throughput drug discovery screens for this class of prote ...

2013

Generation of monoclonal antibody fragments binding the native γ-secretase complex for use in structural studies

Patrick Fraering, Lorène Aeschbach, Claude André Schweizer, Mitko Dimitrov

A detailed understanding of γ-secretase structure is crucially needed to elucidate its unique properties of intramembrane protein cleavage and to design therapeutic compounds for the safe treatment of Alzheimer's disease. γ-Secretase is an enzyme complex c ...

Amer Chemical Soc2012

Alzheimer's Disease-Linked Mutations in Presenilin-1 Result in a Drastic Loss of Activity in Purified gamma-Secretase Complexes

Patrick Fraering, Lorène Aeschbach, Jemila Houacine

Background: Mutations linked to early onset, familial forms of Alzheimer's disease (FAD) are found most frequently in PSEN1, the gene encoding presenilin-1 (PS1). Together with nicastrin (NCT), anterior pharynx-defective protein 1 (APH1), and presenilin en ...

Public Library of Science2012

Selective neutralization of APP-C99 with monoclonal antibodies reduces the production of Alzheimer's Aβ peptides

Patrick Fraering, Lorène Aeschbach, Jemila Houacine, Tristan Bolmont

The toxic amyloid-β (Aβ) peptides involved in Alzheimer's disease (AD) are produced after processing of the amyloid precursor protein-C-terminal fragment APP-C99 by γ-secretase. Thus, major therapeutic efforts have been focused on inhibiting the activity o ...

Elsevier Science Inc2012

Therapeutic antibodies targeting app-c99

Patrick Fraering, Lorène Aeschbach, Jemila Houacine, Tristan Bolmont

The present invention relates to an isolated and/or purified antibody, antibody fragment or derivative thereof able to block the gamma-secretase-dependent processing of the amyloid precursor protein (APP) and to pharmaceutical compositions containing said ...

2012

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

Patrick Fraering, Lorène Aeschbach, 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

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

Patrick Fraering, Lorène Aeschbach, 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