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

Capturing the heterogeneity of alpha-synuclein pathology in synucleinopathies

Synucleinopathies such as Parkinson's disease, dementia with Lewy bodies and multiple system atrophy (MSA) are detrimental neurodegenerative diseases. Alpha-synuclein (aSyn), the main aggregating protein found in the pathological inclusions of these ailmen ...

EPFL2022

Enhancing mitochondrial quality control to fight neuromuscular degeneration in aging and disease

Mario Romani

Loss of mitochondrial function and proteostasis typify aging and age-associated degenerative disorders such as Alzheimer's disease and muscle aging. To date, no cure or preventive measure is available to manage these conditions. Alterations of cellular pro ...

EPFL2021

Molecular dissection of amyloid disaggregation by human HSP70

Paolo De Los Rios, Alessandro Barducci

The molecular steps that lead to the disaggregation of amyloid fibrils are shown to involve the synergistic action of HSP70 and its co-chaperones DNAJB1 and HSP110. ...

NATURE RESEARCH2020

Single-molecule studies of amyloid proteins: from biophysical properties to diagnostic perspectives

Chan Cao

In neurodegenerative diseases, a wide range of amyloid proteins or peptides such as amyloid-beta and alpha-synuclein fail to keep native functional conformations, followed by misfolding and self-assembling into a diverse array of aggregates. The aggregates ...

CAMBRIDGE UNIV PRESS2020

Half a century of amyloids: past, present and future

Raffaele Mezzenga, Hilal Lashuel

Amyloid diseases are global epidemics with profound health, social and economic implications and yet remain without a cure. This dire situation calls for research into the origin and pathological manifestations of amyloidosis to stimulate continued develop ...

Royal Society of Chemistry2020

Anti-Aβ antibodies bound to neuritic plaques enhance microglia activity and mitigate tau pathology

Philippe Colin, Bernard Schneider, Vanessa Laversenne

The brain pathology of Alzheimer’s disease (AD) is characterized by the misfolding and aggregation of both the amyloid beta (Aβ) peptide and hyperphosphorylated forms of the tau protein. Initial Aβ deposition is considered to trigger a sequence of deleteri ...

2020

Nanoscale Characterization of Amyloid Fibrils and Biomacromolecules by Atomic Force Microscopy Approaches

Jiangtao Zhou

This thesis focuses on the interdisciplinary biophysical research field, in which physical approaches are applied to study the biological phenomena. Specifically, the main object of the research in this thesis is to target biological species,especially the ...

EPFL2020

A simple, versatile and robust centrifugation-based filtration protocol for the isolation and quantification of alpha-synuclein monomers, oligomers and fibrils: Towards improving experimental reproducibility in alpha-synuclein research

Hilal Lashuel, Anass Chiki, Sonia Donzelli, Muhammed Muazzam Kamil Syed

Increasing evidence suggests that the process of alpha-synuclein (alpha-syn) aggregation from monomers into amyloid fibrils and Lewy bodies, via oligomeric intermediates plays an essential role in the pathogenesis of different synucleinopathies, including ...

Wiley-Blackwell2020

The Clustering of mApoE Anti-Amyloidogenic Peptide on Nanoparticle Surface Does Not Alter Its Performance in Controlling Beta-Amyloid Aggregation

Francesco Stellacci, Paulo Henrique Jacob Silva

The deposition of amyloid-beta (A beta) plaques in the brain is a significant pathological signature of Alzheimer's disease, correlating with synaptic dysfunction and neurodegeneration. Several compounds, peptides, or drugs have been designed to redirect o ...

2020

Gold nanoparticles as a new tool in amyloid studies

Urszula Beata Cendrowska

The misfolding and self-assembly of proteins into fibrils is a hallmark of several neurodegenerative and systemic diseases. These disease-associated proteins have the propensity to form fibrils with a cross-Î² sheet structure, called amyloids. Amyloids can ...

EPFL2020

Expert recommendation from the Swiss Amyloidosis Network (SAN) for systemic AL-amyloidosis

Alessio Mylonas, Andrea Cavalli, Martin Meyer

Systemic amyloidosis is a heterogeneous group of diseases associated with protein misfolding into insoluble beta-sheet rich structures that deposit extracellularly in different organs, eventually compromising their function. There are more than 30 differen ...

E M H SWISS MEDICAL PUBLISHERS LTD2020

Application of anti-amyloid beta immunization using encapsulated cell technology in mouse models of Alzheimer's disease

Vanessa Laversenne

Alzheimer's disease (AD) is the most common form of dementia in the elderly. AD is characterized by the deposition of two aggregated proteins: Amyloid beta (Aß) and hyperphosphorylated tau. Accumulations of these proteins are thought to be the signature ...

EPFL2019

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 ...

SPRINGER2019

Membrane–Protein–Hydration Interaction of α-Synuclein with Anionic Vesicles Probed via Angle-Resolved Second-Harmonic Scattering

Sylvie Roke, Halil Ibrahim Okur, Jan Dedic

Amyloid formation of the protein α-synuclein promotes neurodegeneration in Parkinson's disease. The normal function of α-synuclein includes synaptic vesicle transport and fusion, and the protein binds strongly to negatively charged vesicles in vitro. Here, ...

2019

GABA and glutamate moderate beta-amyloid related functional connectivity in cognitively unimpaired old-aged adults

Dimitri Nestor Alice Van De Ville, Maria Giulia Preti

Background: Effects of beta-amyloid accumulation on neuronal function precede the clinical manifestation of Alzheimer's disease (AD) by years and affect distinct cognitive brain networks. As previous studies suggest a link between beta-amyloid and dysregul ...

2019

Histidine Targeting Heterobimetallic Ruthenium(II)-Gold(I) Complexes

Paul Joseph Dyson, Daniel Ortiz Trujillo, Lucinda Kate Batchelor

Inspired by the preferential, allosteric binding of RAPTA-T and auranofin to the nucleosome core particle, we describe the design and synthesis of a series of heterobimetallic ruthenium(II)-gold(I) complexes with varying spacer lengths ranging from four to ...

2019

Crosslinking Allosteric Sites on the Nucleosome Core Particle

Lucinda Kate Batchelor

Designing compounds that bind to the acidic patch of the nucleosome core particle (NCP) is an emerging therapeutic approach that can inhibit the binding of key chromatin factors. Pretreatment of human ovarian carcinoma, A2780, cells with RAPTA-T, an antime ...

EPFL2019

Zinc 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 Inc2017

Human Kunitz-type protease inhibitor engineered for enhanced matrix retention extends longevity of fibrin biomaterials

Jeffrey Alan Hubbell, Peter Frey, Kristen Lorentz, Priscilla Suhasna Maithili Briquez, Hans Mattias Larsson

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 ...

2017

Studying membrane-protein interplay by modeling realistic conditions

Martina Audagnotto

Realistic models of cellular environments have long captured the imagination of biologists and physical scientists. More than 20 years ago, Goodshellâ s inspiring rendering of cellular environments provided the foundation for the idea of capturing the ful ...

EPFL2017