Publications associées à Dopamine Transporter, PhosphoSerine129 alpha-Synuclein and alpha-Synuclein Levels in Aged LRRK2 G2019S Knock-In and Knock-Out Mice

Large-scale in-silico analysis of CSF dynamics within the subarachnoid space of the optic nerve

BackgroundImpaired cerebrospinal fluid (CSF) dynamics is involved in the pathophysiology of neurodegenerative diseases of the central nervous system and the optic nerve (ON), including Alzheimer's and Parkinson's disease, as well as frontotemporal dementia ...

BMC2024

Development and validation of an expanded antibody toolset that captures alpha-synuclein pathological diversity in Lewy body diseases

Hilal Lashuel, Melek Firat Altay, Johannes Burtscher, Somanath Jagannath

The abnormal aggregation and accumulation of alpha-synuclein (aSyn) in the brain is a defining hallmark of synucleinopathies. Various aSyn conformations and post-translationally modified forms accumulate in pathological inclusions and vary in abundance amo ...

Nature Portfolio2023

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

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 Relevance of Post-Translationally Modified Alpha-Synuclein (pSer87, pSer129, nTyr39) in Idiopathic Parkinson's Disease and Multiple System Atrophy

Hilal Lashuel, Melek Firat Altay

Aggregated alpha-synuclein (alpha-synuclein) is the main component of Lewy bodies (LBs), Lewy neurites (LNs), and glial cytoplasmic inclusions (GCIs), which are pathological hallmarks of idiopathic Parkinson's disease (IPD) and multiple system atrophy (MSA ...

MDPI2022

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

Tomislav Milekovic, Grégoire Courtine, 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

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

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

Prominent astrocytic alpha-synuclein pathology with unique post-translational modification signatures unveiled across Lewy body disorders

Hilal Lashuel, Melek Firat Altay

Alpha-synuclein (aSyn) is a pre-synaptic monomeric protein that can form aggregates in neurons in Parkinson's disease (PD), Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB), and in oligodendrocytes in multiple system atrophy (MSA ...

BMC2022

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

Reverse engineering Lewy bodies: how far have we come and how far can we go?

Hilal Lashuel, Mohamed Bilal Fares, Somanath Jagannath

Lewy bodies (LBs) are α-synuclein (α-syn)-rich intracellular inclusions that are an important pathological hallmark of Parkinson disease and several other neurodegenerative diseases. Increasing evidence suggests that the aggregation of α-syn has a central ...

2021

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

Hilal Lashuel, Magdalena Zweckstetter

With the advent of the genetic era in Parkinson's disease (PD) research in 1997, alpha-synuclein was identified as an important player in a complex neurodegenerative disease that affects >10 million people worldwide. PD has been estimated to have an econom ...

NATURE RESEARCH2021

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

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

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

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

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

Structure of a D2 dopamine receptor-G-protein complex in a lipid membrane

Mahdi Hijazi, Patrick Daniel Barth

The D2 dopamine receptor (DRD2) is a therapeutic target for Parkinson's disease(1)and antipsychotic drugs(2). DRD2 is activated by the endogenous neurotransmitter dopamine and synthetic agonist drugs such as bromocriptine(3), leading to stimulation of G(i) ...

NATURE PUBLISHING GROUP2020

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