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Alpha-synuclein, especially the Parkinson's disease-associated mutants, forms pore-like annular and tubular protofibrils

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Recently, single-particle cryo-electron microscopy emerged as a technique capable of determining protein structures at near-atomic resolution and resolving protein dynamics with a temporal resolution ranging from second to milliseconds. This thesis describ ...

EPFL2024

Targeting TDP-43 Proteinopathies in Neurodegeneration by its Native-State Stabilization.

Lixin Yang

Preventing the misfolding or aggregation of TDP-43 is the most actively pursued disease-modifying strategy to treat amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. In our work, we provide proof of concept that native state stabili ...

EPFL2024

Molecular mechanism of plasmid elimination by the DdmDE defense system

Melanie Blokesch, Sandrine Stutzmann, David William Adams, Laurie Righi

Seventh pandemic Vibrio cholerae strains contain two pathogenicity islands that encode the DNA defense modules DdmABC and DdmDE. Here we use cryogenic electron microscopy to reveal the mechanistic basis for plasmid defense by DdmDE. A structure of the DdmD ...

2024

Post-translational glycosylation diminishes α-synuclein pathology formation

Hilal Lashuel

O-linked N-acetylglucosamine (O-GlcNAc) is an endogenous form of glycosylation that alters the structure of alpha-synuclein amyloid fibrils and attenuates their pathogenetic properties. The modified fibrils have a significantly reduced ability to seed the ...

Berlin2024

3D reconstruction of curvilinear one-dimensional objects viewed in transmission electron microscopy

Gulnaz Ganeeva

To obtain a more complete understanding of material microstructure at the nanoscale and to gain profound insights into their properties, there is a growing need for more efficient and precise methods that can streamline the process of 3D imaging using a tr ...

EPFL2023

Observing the fast dynamics of nanoscale systems is crucial in order to understand and ultimately control their behavior. Characterizing these dynamic processes requires techniques with atomic spatial resolution and a temporal resolution that matches the t ...

EPFL2023

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TAR DNA-binding protein with 43 kD (TDP-43) is a partially disordered protein that misfolds and accumulates in the brains of patients affected by several neurodegenerative diseases. TDP-43 oligomers have been reported to form due to aberrant misfolding or ...

Washington2023

BigDataProcessor2: a free and open-source Fiji plugin for inspection and processing of TB sized image data

Nicolas René Chiaruttini

Modern bioimaging and related areas such as sensor technology have undergone tremendous development over the last few years. As a result, contemporary imaging techniques, particularly electron microscopy (EM) and light sheet microscopy, can frequently gene ...

OXFORD UNIV PRESS2021

New insights on the structure of alpha-synuclein fibrils using cryo-electron microscopy

Henning Paul-Julius Stahlberg, Dongchun Ni, Ricardo Cesar Guerrero Ferreira

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

Do Lewy bodies contain alpha-synuclein fibrils? and Does it matter? A brief history and critical analysis of recent reports

Hilal Lashuel

Several lines of evidence from neuropathological studies, human genetics, in vitro aggregation studies and cellular and animal models support the hypothesis that aSyn plays a central role in the formation of Lewy pathologies. These are cytoplasmic proteina ...

2020