Alpha-synuclein research: defining strategic moves in the battle against Parkinson's disease

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Publications associées (30)

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, Jean-Christophe Copin, Johannes Burtscher

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

New insights on the structure of alpha-synuclein fibrils using cryo-electron microscopy

Henning Paul-Julius Stahlberg, Ricardo Cesar Guerrero Ferreira, Dongchun Ni

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, Sonia Donzelli, Muhammed Muazzam Kamil Syed

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

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

Dopaminergic neurodegeneration induced by Parkinson's disease-linked G2019S LRRK2 is dependent on kinase and GTPase activity

Darren Moore, Elpida Tsika, Xi Chen

Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of late-onset, autosomal-dominant familial Parkinson's disease (PD). LRRK2 functions as both a kinase and GTPase, and PD-linked mutations are known to influence both enzymatic acti ...

National Academy of Sciences2020

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

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

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

Chronic corticosterone aggravates behavioral and neuronal symptomatology in a mouse model of alpha-synuclein pathology

Maria del Carmen Sandi Perez, Hilal Lashuel, Anass Chiki, Jean-Christophe Copin, João Pedro de Matos Rodrigues, Johannes Burtscher

Debilitating, yet underinvestigated nonmotor symptoms related to mood/emotion, such as depression, are common in Parkinson's disease. Here, we explore the role of depression and of the amygdala, a brain region robustly linked to mood/emotion, in synucleino ...

2019

Phospho-S129 Alpha-Synuclein Is Present in Human Plasma but Not in Cerebrospinal Fluid as Determined by an Ultrasensitive Immunoassay

Hilal Lashuel, Sean Michael Deguire, Lara Petricca

Accumulation and aggregation of misfolded alpha-synuclein is believed to be a cause of Parkinson's disease (PD). Phosphorylation of alpha-synuclein at S129 is known to be associated with the pathological misfolding process, but efforts to investigate the r ...

2019

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

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