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Post-translational glycosylation diminishes α-synuclein pathology formation

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Pathological substrate of memory impairment in multiple system atrophy

Hilal Lashuel, Melek Firat Altay

Aims: Synaptic dysfunction in Parkinson's disease is caused by propagation of pathogenic alpha-synuclein between neurons. Previously, in multiple system atrophy (MSA), pathologically characterised by ectopic deposition of abnormal alpha-synuclein predomina ...

WILEY2022

Effects of sedimentation, microgravity, hydrodynamic mixing and air-water interface on alpha-synuclein amyloid formation

Giovanni Dietler, Giovanni Longo, Francesco Simone Ruggeri, Jiangtao Zhou

The formation of amyloid fibrils is a characterizing feature of a range of protein misfolding diseases, including Parkinson's disease. The propensity of native proteins to form such amyloid fibril, both in vitro and in vivo, is highly sensitive to the surr ...

ROYAL SOC CHEMISTRY2020

A compelling link is emerging between the posttranslational modification O-GlcNAc and protein aggregation. A prime example is alpha-synuclein, which forms toxic aggregates that are associated with neurodegeneration in Parkinson's and related diseases. alph ...

NATL ACAD SCIENCES2019

Amyloid Single Cell Cytotoxicity Assays by Nanomotion Detection

Giovanni Dietler, Hilal Lashuel, Sandor Kasas, Anne-Laure Mahul Mellier, Giovanni Longo, Francesco Simone Ruggeri

Cells are extremely complex systems able to modify actively their metabolism and behaviour in response to environmental conditions and stimuli, such as pathogenic agents or drugs. The comprehension of these responses is central to understand the molecular ...

Springer Nature2017

Fibril growth and seeding capacity play key roles in α-synuclein-mediated apoptotic cell death

Hilal Lashuel, Anne-Laure Mahul Mellier, Nadine Aït Bouziad, Bohumil Maco, Filip Vercruysse

The role of extracellular α-synuclein (α-syn) in the initiation and the spreading of neurodegeneration in Parkinson's disease (PD) has been studied extensively over the past 10 years. However, the nature of the α-syn toxic species and the molecular mechani ...

Nature Publishing Group2015

Alpha-Synuclein Effects at the ER-to-Golgi Level and Potential Biomarkers in Rat Models of the Early Phase of Parkinson's Disease

Philippe Guillaume Coune

While Parkinson's disease has been described nearly 200 years ago, the mechanisms leading to the degeneration of selectively vulnerable populations of neurons, such as dopaminergic neurons in the substantia nigra, remain mostly unknown. Our poor understand ...

EPFL2011

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Parkinson disease (PD) is characterized by dopaminergic neurodegeneration and intracellular inclusions of alpha-synuclein amyloid fibers, which are stable and difficult to dissolve. Whether inclusions are neuroprotective or pathological remains controversi ...

American Society for Clinical Investigation2008

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive degeneration of the dopaminergic nigrostriatal pathway and the abnormal appearance of intracellular inclusions named Lewy bodies (LBs). Over the past few years, the d ...

EPFL2005

Two mutations in the alpha-synuclein gene (A30P and A53T) have been linked to autosomal dominant early-onset Parkinson's disease (PD). Both mutations promote the formation of transient protofibrils (prefibrillar oligomers), suggesting that protofibrils are ...

Elsevier2002