Publications related to Rethinking protein aggregation and drug discovery in neurodegenerative diseases: Why we need to embrace complexity?

Related publications (38)

Effective Inhibition of TDP-43 Aggregation by Native State Stabilization

Preventing the misfolding or aggregation of transactive response DNA binding protein with 43 kDa (TDP-43) is the most actively pursued disease-modifying strategy to treat amyotrophic lateral sclerosis and other neurodegenerative diseases. In this work, we ...

Wiley-VCH Verlag GmbH2024

Method of preparation of amyloidogenic protein aggregates and uses thereof

Hilal Lashuel, Galina Limorenko

The invention relates to methods for the preparation of method of preparation of Tau aggregates, including fibrils, fibrillar species, soluble and insoluble oligomeric species, new Tau aggregates and uses thereof. The invention further relates to the uses ...

2024

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

Development and clinical validation of computational imaging biomarkers for neurodegenerative diseases

Veronica Lily Ravano

Neurodegenerative and neuroinflammatory disorders often involve complex pathophysiological mechanisms that are â to this date â only partially understood. A more comprehensive understanding of those microstructural processes and their characterization ...

EPFL2024

Deconstructing and Reconstructing the Complexity of Tau pathology

Galina Limorenko

This thesis consists of four Chapters unified by a singular theme â how do we develop disease models that faithfully reproduce the pathology seen in patients suffering from neurodegenerative disorders associated with the Tau protein, such as Alzheimerâ ...

EPFL2023

Fully co-factor-free ClearTau platform produces seeding-competent Tau fibrils for reconstructing pathological Tau aggregates

Hilal Lashuel, Henning Paul-Julius Stahlberg, Galina Limorenko, Rajasekhar Kolla, Meltem Tatli

The authors report a method for producing co-factor-free fibrils from all full-length Tau isoforms. The method paves the way for reconstituting pathology resembling Tau fibrils and enables screening of Tau aggregation-modifying compounds for targeted thera ...

Nature Research2023

VPS35 and α-Synuclein fail to interact to modulate neurodegeneration in rodent models of Parkinson's disease

Elpida Tsika

BackgroundMutations in the vacuolar protein sorting 35 ortholog (VPS35) gene cause late-onset, autosomal dominant Parkinson's disease (PD), with a single missense mutation (Asp620Asn, D620N) known to segregate with disease in families with PD. The VPS35 ge ...

BMC2023

Salivary Proteomics Identifies Transthyretin as a Biomarker of Early Dementia Conversion

Adrian Schmid

Background: Alzheimer's disease (AD) remains to date an incurable disease with a long asymptomatic phase. Early diagnosis in peripheral biofluids has emerged as key for identifying subjects at risk and developing therapeutics and preventative approaches. ...

IOS PRESS2022

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

Trans‐seeding of Alzheimer‐related tau protein by a yeast prion

Henning Paul-Julius Stahlberg

Abnormal tau protein aggregates constitute a hallmark of Alzheimer's disease. The mechanisms underlying the initiation of tau aggregation in sporadic neurodegeneration remain unclear. Here we investigate whether a non-human prion can seed tau aggregation. ...

2022

Alpha-synuclein as a Potential Biomarker for Parkinson’s Disease and Other Synucleinopathies: Gaps, Challenges, and Opportunities

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 ...

2022

Tau seeds from patients induce progressive supranuclear palsy pathology and symptoms in primates

Grégoire Courtine, Tomislav Milekovic, Flavio Raschella

Progressive supranuclear palsy is a primary tauopathy affecting both neurons and glia and is responsible for both motor and cognitive symptoms. Recently, it has been suggested that progressive supranuclear palsy tauopathy may spread in the brain from cell ...

OXFORD UNIV PRESS2022

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

Towards elucidating the structural and cellular determinants of a-synuclein seeding and toxicity

Somanath Jagannath

Although it has been nearly two and half decades since the discovery of alpha-synuclein (aSyn) as the major component of Lewy bodies (LBs), our understanding of the involvement of different aSyn species, their seeding, spreading and toxicity in Parkinson's ...

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

Fading of brain network fingerprint in Parkinson's disease predicts motor clinical impairment

Enrico Amico

The clinical connectome fingerprint (CCF) was recently introduced as a way to assess brain dynamics. It is an approach able to recognize individuals, based on the brain network. It showed its applicability providing network features used to predict the cog ...

Wiley2023

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

Structural strains of misfolded tau protein define different diseases

Henning Paul-Julius Stahlberg

In diseases called tauopathies, misfolded tau proteins form aggregates called fibrils. Fibrils from nine different tauopathies show that tau misfolds in many ways, enabling the diseases to be classified according to fibril structure. ...

2021

Investigating receptor-mediated antibody transcytosis using blood-brain barrier organoid arrays

Nathalie Brandenberg, Camilla Carla Alma Ceroni

Background The pathways that control protein transport across the blood-brain barrier (BBB) remain poorly characterized. Despite great advances in recapitulating the human BBB in vitro, current models are not suitable for systematic analysis of the molecul ...

BMC2021

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 ...

2020