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

Publications associées (19)

Nanoplasmonic infrared biosensors enabling detection of misfolded protein biomarkers and drug screening for neurodegenerative diseases

Neurodegenerative diseases (NDDs), such as Parkinson's disease and Alzheimer's disease present a significant global health concern. The misfolding of proteins from native disordered monomeric forms into beta-sheet enriched aggregates of oligomers and fibri ...

EPFL2025

Longitudinal changes in MEG-based brain network topology of ALS patients with cognitive/behavioral impairment—An exploratory study

Alessandra Griffa

Amyotrophic lateral sclerosis (ALS) with only motor impairment (ALS-pure motor) and the behavioral variant of frontotemporal dementia (bvFTD) are hypothesized to represent extreme ends of a disease spectrum, which encompasses ALS with cognitive/behavioral ...

MIT Press2025

Exploring the therapeutic potential of Huntingtin native state stabilization through targeting its interacting partners

Enzo Sébastien Benjamin Morro

Huntington's disease (HD) is a devastating neurodegenerative disorder marked by the accumulation of Huntingtin protein (HTT) fragments in HD neuronal cells. These aggregates are predominantly composed of polyglutamine (polyQ)-containing HTT N-terminal frag ...

EPFL2024

Ultrastructural characterization of tau pathology in the human post‐mortem Alzheimer’s disease brain

Louis Travers, Philippine Laure Diane Schneider, Eglantine Vialaneix, Henning Paul-Julius Stahlberg, Amanda Jennifer Lewis

Neuropathological tau tangles in Alzerheimer’s disease (AD) have been roughly characterized into pre‐tangles, mature tangles and ghost tangles. However, to date, their maturation in the human brain is poorly understood. Here, we aimed to define the structu ...

Wiley2024

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

Fast Self-Assembly Dynamics of a beta-Sheet Peptide Soft Material

Sandor Kasas

Peptide-based hydrogels are promising biocompatible materials for wound healing, drug delivery, and tissue engineering applications. The physical properties of these nanostructured materials depend strongly on the morphology of the gel network. However, th ...

WILEY-V C H VERLAG GMBH2023

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

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

Hilal Lashuel, Anne-Laure Mahul Mellier, Pedro José Santana Ribeiro Magalhães, Sonia Donzelli, Ramanath Narayana Hegde

The alpha-synuclein mutation E83Q, the first in the NAC domain of the protein, was recently identified in a patient with dementia with Lewy bodies. We investigated the effects of this mutation on the aggregation of aSyn monomers and the structure, morpholo ...

AMER ASSOC ADVANCEMENT SCIENCE2022

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

An integrative approach to elucidate the mechanisms and dynamics of Huntingtin aggregation and inclusion formation in neuronal models of Huntington's Disease

Nathan Alain Denis Riguet

Despite the fact that the gene responsible for Huntington's disease (HD) is known, we still do not understand the underlying mechanisms leading to neurodegeneration and death. Identifying and understanding the mechanisms controlling mutant huntingtin (mHtt ...

EPFL2022

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

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

An integrative multi-omics approach reveals new central nervous system pathway alterations in Alzheimer's disease

Christopher Clark

Background Multiple pathophysiological processes have been described in Alzheimer's disease (AD). Their inter-individual variations, complex interrelations, and relevance for clinical manifestation and disease progression remain poorly understood. We hypot ...

2021

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

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

Toward an objective assessment of mobility in clinical and daily activity settings

Arash Atrsaei

Quantification of mobility is the key to monitor the progression of mobility disorders as well as the effect of an intervention. Inertial measurement units (IMUs) with dedicated algorithms can quantify postural transitions and gait as the two key aspects o ...

EPFL2021