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

Publications associées (29)

Deconstructing and Reconstructing the Complexity of Tau pathology

This thesis consists of four Chapters unified by a singular theme â how do we develop disease models that faithfully reproduce the pathology seen in patients suffering from neurodegenerative disorders associated with the Tau protein, such as Alzheimerâ ...

EPFL2023

Dynamics of the most common pathogenic mtDNA variant m.3243A > G demonstrate frequency-dependency in blood and positive selection in the germline

Konstantin Popadin

The A-to-G point mutation at position 3243 in the human mitochondrial genome (m.3243A > G) is the most common pathogenic mtDNA variant responsible for disease in humans. It is widely accepted that m.3243A > G levels decrease in blood with age, and an age c ...

Oxford University Press2022

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

Lewy body-associated proteins: Victims, instigators, or innocent bystanders? The case of AIMP2 and alpha-synuclein

Hilal Lashuel, Salvatore Novello

Lewy bodies (LBs), one of the neuropathological defining hallmarks of Parkinson's disease (PD), are composed of a complex mixture of alpha-synuclein (aSyn) filaments and hundreds of proteins, lipids, and membranous organelles. However, these proteins' role ...

2021

NAD+ boosting reduces age-associated amyloidosis and restores mitochondrial homeostasis in muscle

Changmyung Oh, Johan Auwerx, Hongbo Zhang, Hao Li, Vincenzo Sorrentino, Tanes Imamura de Lima, Mario Romani

Aging is characterized by loss of proteostasis and mitochondrial homeostasis. Here, we provide bioinformatic evidence of dysregulation of mitochondrial and proteostasis pathways in muscle aging and diseases. Moreover, we show accumulation of amyloid-like d ...

2021

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

Half a century of amyloids: past, present and future

Hilal Lashuel, Raffaele Mezzenga

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

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

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, Muhammed Muazzam Kamil Syed, Sonia Donzelli

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

Oligomerization Profile of Human Transthyretin Variants with Distinct Amyloidogenicity

Bruno Emanuel Ferreira De Sousa Correia

One of the molecular hallmarks of amyloidoses is ordered protein aggregation involving the initial formation of soluble protein oligomers that eventually grow into insoluble fibrils. The identification and characterization of molecular species critical for ...

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

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

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

Unraveling the complexity of amyloid polymorphism using gold nanoparticles and cryo-EM

Francesco Stellacci, Hilal Lashuel, Paulo Henrique Jacob Silva, Anass Chiki, Nadine Aït Bouziad, Urszula Beata Cendrowska, Zekiye Pelin Güven, Senthil Kumar Thangaraj, Sophie Vieweg

Increasing evidence suggests that amyloid polymorphism gives rise to different strains of amyloids with distinct toxicities and pathology-spreading properties. Validating this hypothesis is challenging due to a lack of tools and methods that allow for the ...

National Academy of Sciences2020

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

Andrea Cavalli, Alessio Mylonas

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

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

Bernard Schneider, Philippe André Guy Colin, 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 ...

BioMed Central2020

Diffusion MRI biomarkers of white matter microstructure vary nonmonotonically with increasing cerebral amyloid deposition

Ileana Ozana Jelescu

Beta amyloid (A beta) accumulation is the earliest pathological marker of Alzheimer's disease (AD), but early AD pathology also affects white matter (WM) integrity. We performed a cross-sectional study including 44 subjects (23 healthy controls and 21 mild ...

2020

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

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

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

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

Sylvie Roke, Jan Dedic, Halil Ibrahim Okur

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