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

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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

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 ...

2020

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Fibrils of alpha-synuclein are significant components of cellular inclusions associated with several neuropathological disorders including Parkinson’s disease, multiple system atrophy and dementia with Lewy bodies. In recent years, technological advances i ...

2020

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

Two new polymorphic structures of human full-length alpha-synuclein fibrils solved by cryo-electron microscopy

Henning Paul-Julius Stahlberg, Ricardo Cesar Guerrero Ferreira, Pratibha Kumari

Intracellular inclusions rich in alpha-synuclein are a hallmark of several neuropathological diseases including Parkinson’s disease (PD). Previously, we reported the structure of alpha-synuclein fibrils (residues 1–121), composed of two protofibrils that a ...

2019

Cryo-EM structure of alpha-synuclein fibrils

Henning Paul-Julius Stahlberg, Ricardo Cesar Guerrero Ferreira

Parkinson's disease is a progressive neuropathological disorder that belongs to the class of synucleinopathies, in which the protein alpha-synuclein is found at abnormally high concentrations in affected neurons. Its hallmark are intracellular inclusions c ...

eLife Sciences Publications, Ltd2018

Methods of treating amyloid-beta peptide diseases

Johan Auwerx, Laurent Mouchiroud, Vincenzo Sorrentino

The present invention is directed to a method of treating an amyloid-3 peptide disease in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound that enhances mitochondrial proteostasi ...

2018

Amyloid polymorphism of twisted and straight beta-endorphin fibrils was studied by negative-stain transmission electron microscopy, scanning transmission electron microscopy, and solid-state nuclear magnetic resonance spectroscopy. Whereas fibrils assemble ...

American Chemical Society (ACS)2017

Discriminative adsorption of amphiphilic monolayer protected gold nanoparticles on amyloid fibers

Paulo Henrique Jacob Silva

This thesis presents a systematic study of how different types monolayer-protected AuNPs interact with amyloid fibers. We report a class of amphiphilic gold nanoparticles capable of adsorbing onto specific surface features on these types of protein fibers. ...

EPFL2016

A critical concentration of N-terminal pyroglutamylated amyloid beta drives the misfolding of Ab1-42 into more toxic aggregates

Giovanni Dietler, Francesco Simone Ruggeri

A wide consensus based on robust experimental evidence indicates pyroglutamylated amyloid-beta isoform (A beta pE3-42) as one of the most neurotoxic peptides involved in the onset of Alzheimer's disease. Furthermore, A beta pE3-42 co-oligomerized with exce ...

Elsevier2016