α-Synuclein conformers reveal link to clinical heterogeneity of α-synucleinopathies

Abstract α-Synucleinopathies, such as Parkinson’s disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy, are a class of neurodegenerative diseases exhibiting intracellular inclusions of misfolded α-synuclein (αSyn), referred to as Lewy bodies or oligodendroglial cytoplasmic inclu...

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Main Authors: Matthias Schmitz, Niccolò Candelise, Sezgi Canaslan, Hermann C. Altmeppen, Jakob Matschke, Markus Glatzel, Neelam Younas, Saima Zafar, Peter Hermann, Inga Zerr
Format: Article
Language:English
Published: BMC 2023-03-01
Series:Translational Neurodegeneration
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Online Access:https://doi.org/10.1186/s40035-023-00342-4
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author Matthias Schmitz
Niccolò Candelise
Sezgi Canaslan
Hermann C. Altmeppen
Jakob Matschke
Markus Glatzel
Neelam Younas
Saima Zafar
Peter Hermann
Inga Zerr
author_facet Matthias Schmitz
Niccolò Candelise
Sezgi Canaslan
Hermann C. Altmeppen
Jakob Matschke
Markus Glatzel
Neelam Younas
Saima Zafar
Peter Hermann
Inga Zerr
author_sort Matthias Schmitz
collection DOAJ
description Abstract α-Synucleinopathies, such as Parkinson’s disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy, are a class of neurodegenerative diseases exhibiting intracellular inclusions of misfolded α-synuclein (αSyn), referred to as Lewy bodies or oligodendroglial cytoplasmic inclusions (Papp–Lantos bodies). Even though the specific cellular distribution of aggregated αSyn differs in PD and DLB patients, both groups show a significant pathological overlap, raising the discussion of whether PD and DLB are the same or different diseases. Besides clinical investigation, we will focus in addition on methodologies, such as protein seeding assays (real-time quaking-induced conversion), to discriminate between different types of α-synucleinopathies. This approach relies on the seeding conversion properties of misfolded αSyn, supporting the hypothesis that different conformers of misfolded αSyn may occur in different types of α-synucleinopathies. Understanding the pathological processes influencing the disease progression and phenotype, provoked by different αSyn conformers, will be important for a personalized medical treatment in future.
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spelling doaj.art-6c54b68df0764b89832328706fb2e6202023-03-22T12:12:47ZengBMCTranslational Neurodegeneration2047-91582023-03-0112111110.1186/s40035-023-00342-4α-Synuclein conformers reveal link to clinical heterogeneity of α-synucleinopathiesMatthias Schmitz0Niccolò Candelise1Sezgi Canaslan2Hermann C. Altmeppen3Jakob Matschke4Markus Glatzel5Neelam Younas6Saima Zafar7Peter Hermann8Inga Zerr9Department of Neurology, National Reference Center for TSE, The German Center for Neurodegenerative Diseases (DZNE), Georg-August-University, University Medicine GottingenNational Center for Drug Research and Evaluation, Institute Superiore di SanitàDepartment of Neurology, National Reference Center for TSE, The German Center for Neurodegenerative Diseases (DZNE), Georg-August-University, University Medicine GottingenInstitute of Neuropathology, University Medical Center Hamburg-Eppendorf (UKE)Institute of Neuropathology, University Medical Center Hamburg-Eppendorf (UKE)Institute of Neuropathology, University Medical Center Hamburg-Eppendorf (UKE)Department of Neurology, National Reference Center for TSE, The German Center for Neurodegenerative Diseases (DZNE), Georg-August-University, University Medicine GottingenDepartment of Neurology, National Reference Center for TSE, The German Center for Neurodegenerative Diseases (DZNE), Georg-August-University, University Medicine GottingenDepartment of Neurology, National Reference Center for TSE, The German Center for Neurodegenerative Diseases (DZNE), Georg-August-University, University Medicine GottingenDepartment of Neurology, National Reference Center for TSE, The German Center for Neurodegenerative Diseases (DZNE), Georg-August-University, University Medicine GottingenAbstract α-Synucleinopathies, such as Parkinson’s disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy, are a class of neurodegenerative diseases exhibiting intracellular inclusions of misfolded α-synuclein (αSyn), referred to as Lewy bodies or oligodendroglial cytoplasmic inclusions (Papp–Lantos bodies). Even though the specific cellular distribution of aggregated αSyn differs in PD and DLB patients, both groups show a significant pathological overlap, raising the discussion of whether PD and DLB are the same or different diseases. Besides clinical investigation, we will focus in addition on methodologies, such as protein seeding assays (real-time quaking-induced conversion), to discriminate between different types of α-synucleinopathies. This approach relies on the seeding conversion properties of misfolded αSyn, supporting the hypothesis that different conformers of misfolded αSyn may occur in different types of α-synucleinopathies. Understanding the pathological processes influencing the disease progression and phenotype, provoked by different αSyn conformers, will be important for a personalized medical treatment in future.https://doi.org/10.1186/s40035-023-00342-4α-synucleinopathiesα-synucleinRT-QuICProtein strains
spellingShingle Matthias Schmitz
Niccolò Candelise
Sezgi Canaslan
Hermann C. Altmeppen
Jakob Matschke
Markus Glatzel
Neelam Younas
Saima Zafar
Peter Hermann
Inga Zerr
α-Synuclein conformers reveal link to clinical heterogeneity of α-synucleinopathies
Translational Neurodegeneration
α-synucleinopathies
α-synuclein
RT-QuIC
Protein strains
title α-Synuclein conformers reveal link to clinical heterogeneity of α-synucleinopathies
title_full α-Synuclein conformers reveal link to clinical heterogeneity of α-synucleinopathies
title_fullStr α-Synuclein conformers reveal link to clinical heterogeneity of α-synucleinopathies
title_full_unstemmed α-Synuclein conformers reveal link to clinical heterogeneity of α-synucleinopathies
title_short α-Synuclein conformers reveal link to clinical heterogeneity of α-synucleinopathies
title_sort α synuclein conformers reveal link to clinical heterogeneity of α synucleinopathies
topic α-synucleinopathies
α-synuclein
RT-QuIC
Protein strains
url https://doi.org/10.1186/s40035-023-00342-4
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