Publications related to A NAC domain mutation (E83Q) unlocks the pathogenicity of human alpha-synuclein and recapitulates its pathological diversity

Related publications (24)

O-GlcNAc forces an α-synuclein amyloid strain with notably diminished seeding and pathology

Amyloid-forming proteins such alpha-synuclein and tau, which are implicated in Alzheimer's and Parkinson's disease, can form different fibril structures or strains with distinct toxic properties, seeding activities and pathology. Understanding the determin ...

Nature Portfolio2024

Overexpression of human alpha-Synuclein leads to dysregulated microbiome/metabolites with ageing in a rat model of Parkinson disease

Joan Romani Aumedes, Hilal Lashuel, Yogesh Singh Chauhan, Florian Lang

Background Braak's hypothesis states that sporadic Parkinson's disease (PD) follows a specific progression of pathology from the peripheral to the central nervous system, and this progression can be monitored by detecting the accumulation of alpha-Synuclei ...

BMC2023

Degradation of EEG microstates patterns in subjective cognitive decline and mild cognitive impairment: Early biomarkers along the Alzheimer's Disease continuum?

Silvestro Micera

Alzheimer's disease (AD) pathological changes may begin up to decades earlier than the appearance of the first symptoms of cognitive decline. Subjective cognitive decline (SCD) could be the first pre-clinical sign of possible AD, which might be followed by ...

ELSEVIER SCI LTD2023

Capturing the heterogeneity of alpha-synuclein pathology in synucleinopathies

Melek Firat Altay

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

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

Opportunities and challenges of alpha-synuclein as a potential biomarker for Parkinson's disease and other synucleinopathies

Hilal Lashuel, Pedro José Santana Ribeiro Magalhães

Parkinson's disease (PD), the second most common progressive neurodegenerative disease, develops and progresses for 10-15 years before the clinical diagnostic symptoms of the disease are manifested. Furthermore, several aspects of PD pathology overlap with ...

NATURE PORTFOLIO2022

Retromer deficiency in Tauopathy models enhances the truncation and toxicity of Tau

Graham Knott, Evelyne Ruchti, Catherine Maclachlan, Brian Donal McCabe, Wei Jiao, Greta Limoni

Alteration of the levels, localization or post-translational processing of the microtubule associated protein Tau is associated with many neurodegenerative disorders. Here we develop adult-onset models for human Tau (hTau) toxicity in Drosophila that enabl ...

Nature Portfolio2022

Systemic and central nervous system neuroinflammatory signatures of neuropsychiatric symptoms and related cognitive decline in older people

Loïc Dayon

Background Neuroinflammation may contribute to psychiatric symptoms in older people, in particular in the context of Alzheimer's disease (AD). We sought to identify systemic and central nervous system (CNS) inflammatory alterations associated with neuropsy ...

BMC2022

To target Tau pathologies, we must embrace and reconstruct their complexities

Hilal Lashuel, Galina Limorenko

The accumulation of hyperphosphorylated fibrillar Tau aggregates in the brain is one of the defining hallmarks of Tauopathy diseases, including Alzheimer's disease. However, the primary events or molecules responsible for initiation of the pathological Tau ...

ACADEMIC PRESS INC ELSEVIER SCIENCE2021

Clinical correlates of white matter lesions in Parkinson's disease using automated multi-modal segmentation measures

Tobias Kober, Bénédicte Marie Maréchal

Background: Age-related white matter lesions (WML) are common, impact neuronal connectivity, and affect motor function and cognition. In addition to pathological nigrostriatal losses, WML are also common co morbidities in Parkinson's disease (PD) that affe ...

ELSEVIER2021

Enforced dimerization between XBP1s and ATF6f enhances the protective effects of the UPR in models of neurodegeneration

Hilal Lashuel, Sonia Donzelli

Alteration to endoplasmic reticulum (ER) proteostasis is observed in a variety of neurodegenerative diseases associated with abnormal protein aggregation. Activation of the unfolded protein response (UPR) enables an adaptive reaction to recover ER proteost ...

2021

The integrated stress response contributes to tRNA synthetase-associated peripheral neuropathy

Yu Bai, René Uwe Schneider, Cédric Gobet

Dominant mutations in ubiquitously expressed transfer RNA (tRNA) synthetase genes cause axonal peripheral neuropathy, accounting for at least six forms of Charcot-Marie-Tooth (CMT) disease. Genetic evidence in mouse and Drosophila models suggests a gain-of ...

American Association for the Advancement of Science2021

Pharmacological characterization of mutant huntingtin aggregate-directed PET imaging tracer candidates

Hilal Lashuel, Anass Chiki

Huntington's disease (HD) is caused by a CAG trinucleotide repeat expansion in the first exon of the huntingtin (HTT) gene coding for the huntingtin (HTT) protein. The misfolding and consequential aggregation of CAG-expanded mutant HTT (mHTT) underpin HD p ...

Nature Portfolio2021

Membrane-protein-hydration interaction of alpha-synuclein with anionic vesicles in solution probed via angle-resolved second harmonic scattering

Sylvie Roke, Jan Dedic

AMER CHEMICAL SOC2019

alpha-Synuclein O-GlcNAcylation alters aggregation and toxicity, revealing certain residues as potential inhibitors of Parkinson's disease

Hilal Lashuel, Anne-Laure Mahul Mellier

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 ...

National Academy of Sciences2019

Zinc and Copper Differentially Modulate Amyloid Precursor Protein Processing by -Secretase and Amyloid- Peptide Production

Patrick Fraering, Mitko Dimitrov, Hermeto Gerber

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

Mapping mitochondrial heteroplasmy in a Leydig tumor by laser capture microdissection and cycling temperature capillary electrophoresis

Stephan Morgenthaler, Paul Refinetti

Background: The growth of tumor cells is accompanied by mutations in nuclear and mitochondrial genomes creating marked genetic heterogeneity. Tumors also contain non-tumor cells of various origins. An observed somatic mitochondrial mutation would have occu ...

BioMed Central2017

A Balance between Inhibitor Binding and Substrate Processing Confers Influenza Drug Resistance

Jeffrey David Jensen, Claudia Bank

The therapeutic benefits of the neuraminidase (NA) inhibitor oseltamivir are dampened by the emergence of drug resistance mutations in influenza A virus (IAV). To investigate the mechanistic features that underlie resistance, we developed an approach to qu ...

Academic Press Ltd- Elsevier Science Ltd2016

An evaluation of volume-based morphometry for prediction of mild cognitive impairment and Alzheimer's disease

Reto Meuli, Meritxell Bach Cuadra, Alessandro Daducci, Gunnar Krüger, Cristina Granziera, Bénédicte Marie Maréchal, Daniel Andreas Schmitter, Alexis Roche, Delphine Ribes Lemay

Voxel-based morphometry from conventional T1-weighted images has proved effective to quantify Alzheimer’s disease (AD) related brain atrophy and to enable fairly accurate automated classification of AD patients, mild cognitive impaired patients (MCI) and e ...

Elsevier2015

Probing the Unfolded Configurations of a β-Hairpin Using Sketch-Map

Michele Ceriotti

This work examines the conformational ensemble involved in beta-hairpin folding by means of advanced molecular dynamics simulations and dimensionality reduction. A fully atomistic description of the protein and the surrounding solvent molecules is used, an ...

2015