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

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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

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

Enrico Amico, Antonella Romano

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

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

Simulating the progression of brain structural alterations in Parkinson's disease

Chang-Hyun Park

Considering brain structural alterations as neurodegenerative consequences of Parkinson's disease (PD), we sought to infer the progression of PD via the ordering of brain structural alterations from cross-sectional MRI observations. Having measured cortica ...

NATURE PORTFOLIO2022

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

Comparative Analysis of Total Alpha-Synuclein (alpha SYN) Immunoassays Reveals That They Do Not Capture the Diversity of Modified alpha SYN Proteoforms

Hilal Lashuel, Lorène Aeschbach, Mohamed Bilal Fares, Lara Petricca, Ritwik Burai, Layane Hanna-el-Daher

Background: The development of therapeutics for Parkinson's disease (PD) requires the establishment of biomarker assays to enable stratifying patients, monitoring disease progression, and assessing target engagement. Attempts to develop diagnostic assays b ...

IOS PRESS2022

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

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

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

Revisiting the specificity and ability of phospho-S129 antibodies to capture alpha-synuclein biochemical and pathological diversity

Hilal Lashuel, Nicolas Jean Philippe Guex, Christian Iseli, Anne-Laure Mahul Mellier, Jonathan Jean-Pierre Ricci, Yllza Jasiqi, Anass Chiki, Sean Michael Deguire, Ritwik Burai, Melek Firat Altay

Antibodies against phosphorylated alpha-synuclein (aSyn) at 5129 have emerged as the primary tools to investigate, monitor, and quantify aSyn pathology in the brain and peripheral tissues of patients with Parkinson's disease and other neurodegenerative dis ...

NATURE PORTFOLIO2022

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