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Related publications (31)

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Fatal attraction-The role of hypoxia when alpha-synuclein gets intimate with mitochondria

Hilal Lashuel, Grégoire Millet, Johannes Burtscher, Muhammed Muazzam Kamil Syed

Alpha-synuclein aggregation and mitochondrial dysfunction are main pathological hallmarks of Parkinson's disease (PD) and several other neurodegenerative diseases, collectively known as synucleinopathies. However, increasing evidence suggests that they may ...

ELSEVIER SCIENCE INC2021

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

The process of Lewy body formation, rather than simply α-synuclein fibrillization, is one of the major drivers of neurodegeneration

Hilal Lashuel, Graham Knott, Johannes Burtscher, Marion Leleu, Fabien Kuttler, Mary-Claude Croisier-Coeytaux, Anne-Laure Mahul Mellier, Niran Maharjan, Laura Emmeline H Weerens

Parkinson’s disease (PD) is characterized by the accumulation of misfolded and aggregated α-synuclein (α-syn) into intraneuronal inclusions named Lewy bodies (LBs). Although it is widely believed that α-syn plays a central role in the pathogenesis of PD, t ...

National Academy of Sciences2020

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

A simple, versatile and robust centrifugation-based filtration protocol for the isolation and quantification of alpha-synuclein monomers, oligomers and fibrils: Towards improving experimental reproducibility in alpha-synuclein research

Hilal Lashuel, Anass Chiki, Muhammed Muazzam Kamil Syed, Sonia Donzelli

Increasing evidence suggests that the process of alpha-synuclein (alpha-syn) aggregation from monomers into amyloid fibrils and Lewy bodies, via oligomeric intermediates plays an essential role in the pathogenesis of different synucleinopathies, including ...

Wiley-Blackwell2020

Pronounced α-synuclein pathology in a seeding-based mouse model is not sufficient to induce mitochondrial respiration deficits in the striatum and amygdala

Maria del Carmen Sandi Perez, Hilal Lashuel, Johannes Burtscher, Jean-Christophe Copin

Increasing evidence suggests that crosstalk between α-synuclein pathology formation and mitochondrial dysfunction plays a central role in the pathogenesis of Parkinson’s disease and related synucleinopathies. While mitochondrial dysfunction is a well-studi ...

2020

Molecular dissection of amyloid disaggregation by human HSP70

Paolo De Los Rios, Alessandro Barducci

The molecular steps that lead to the disaggregation of amyloid fibrils are shown to involve the synergistic action of HSP70 and its co-chaperones DNAJB1 and HSP110. ...

NATURE RESEARCH2020

How specific are the conformation-specific α-synuclein antibodies? Characterization and validation of 16 α-synuclein conformation-specific antibodies using well-characterized preparations of α-synuclein monomers, fibrils and oligomers with distinct structures and morphology

Hilal Lashuel, Somanath Jagannath, Senthil Kumar Thangaraj

Increasing evidence suggests that alpha-synuclein (α-syn) oligomers are obligate intermediates in the pathway involved in α-syn fibrillization and Lewy body (LB) formation, and may also accumulate within LBs in Parkinson's disease (PD) and other synucleino ...

2020

Discovery of 2-(4-(2-fluoroethoxy)piperidin-1-yl)-9-methyl-9H-pyrrolo[2,3-b:4,5-c']dipyridine ([18F]PI-2014) as PET tracer for the detection of pathological aggregated tau in Alzheimer's disease and other tauopathies

Andrea Pfeifer

The compound screening was initiated with a direct staining assay to identify compounds binding to Tau aggregates and not Abeta plaques using human brain sections derived from late stage Alzheimer's disease donors. The binding of Tau aggregate selective co ...

ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER2020

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

Phosphorylation of α-synuclein is crucial in compensating for proteasomal dysfunction

Hilal Lashuel

α-Synuclein can be degraded by both the ubiquitin-proteasomal system and the chaperone-lysosomal system. However, the switching mechanism between the two pathways is not clearly understood. In our study, we investigated the mutual association between the b ...

Academic Press Inc Elsevier Science2012