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Beyond Strains: Molecular Diversity in Alpha-Synuclein at the Center of Disease Heterogeneity

Alpha-synucleinopathies (α-synucleinopathies) such as Parkinson’s disease (PD), Parkinson’s disease dementia (PDD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA) are all characterized by aggregates of alpha-synuclein (α-syn), but display heterogeneous clinical and pathological p...

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Autores principales: Wojewska, Marcelina J., Otero-Jimenez, Maria, Guijarro-Nuez, Jose, Alegre-Abarrategui, Javier
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10487421/
https://www.ncbi.nlm.nih.gov/pubmed/37686005
http://dx.doi.org/10.3390/ijms241713199
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author Wojewska, Marcelina J.
Otero-Jimenez, Maria
Guijarro-Nuez, Jose
Alegre-Abarrategui, Javier
author_facet Wojewska, Marcelina J.
Otero-Jimenez, Maria
Guijarro-Nuez, Jose
Alegre-Abarrategui, Javier
author_sort Wojewska, Marcelina J.
collection PubMed
description Alpha-synucleinopathies (α-synucleinopathies) such as Parkinson’s disease (PD), Parkinson’s disease dementia (PDD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA) are all characterized by aggregates of alpha-synuclein (α-syn), but display heterogeneous clinical and pathological phenotypes. The mechanism underlying this heterogeneity is thought to be due to diversity in the α-syn strains present across the diseases. α-syn obtained from the post-mortem brain of patients who lived with these conditions is heterogenous, and displays a different protease sensitivity, ultrastructure, cytotoxicity, and seeding potential. The primary aim of this review is to summarize previous studies investigating these concepts, which not only reflect the idea of different syn strains being present, but demonstrate that each property explains a small part of a much larger puzzle. Strains of α-syn appear at the center of the correlation between α-syn properties and the disease phenotype, likely influenced by external factors. There are considerable similarities in the properties of disease-specific α-syn strains, but MSA seems to consistently display more aggressive traits. Elucidating the molecular underpinnings of heterogeneity amongst α-synucleinopathies holds promise for future clinical translation, allowing for the development of personalized medicine approaches tackling the root cause of each α-synucleinopathy.
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spelling pubmed-104874212023-09-09 Beyond Strains: Molecular Diversity in Alpha-Synuclein at the Center of Disease Heterogeneity Wojewska, Marcelina J. Otero-Jimenez, Maria Guijarro-Nuez, Jose Alegre-Abarrategui, Javier Int J Mol Sci Review Alpha-synucleinopathies (α-synucleinopathies) such as Parkinson’s disease (PD), Parkinson’s disease dementia (PDD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA) are all characterized by aggregates of alpha-synuclein (α-syn), but display heterogeneous clinical and pathological phenotypes. The mechanism underlying this heterogeneity is thought to be due to diversity in the α-syn strains present across the diseases. α-syn obtained from the post-mortem brain of patients who lived with these conditions is heterogenous, and displays a different protease sensitivity, ultrastructure, cytotoxicity, and seeding potential. The primary aim of this review is to summarize previous studies investigating these concepts, which not only reflect the idea of different syn strains being present, but demonstrate that each property explains a small part of a much larger puzzle. Strains of α-syn appear at the center of the correlation between α-syn properties and the disease phenotype, likely influenced by external factors. There are considerable similarities in the properties of disease-specific α-syn strains, but MSA seems to consistently display more aggressive traits. Elucidating the molecular underpinnings of heterogeneity amongst α-synucleinopathies holds promise for future clinical translation, allowing for the development of personalized medicine approaches tackling the root cause of each α-synucleinopathy. MDPI 2023-08-25 /pmc/articles/PMC10487421/ /pubmed/37686005 http://dx.doi.org/10.3390/ijms241713199 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Wojewska, Marcelina J.
Otero-Jimenez, Maria
Guijarro-Nuez, Jose
Alegre-Abarrategui, Javier
Beyond Strains: Molecular Diversity in Alpha-Synuclein at the Center of Disease Heterogeneity
title Beyond Strains: Molecular Diversity in Alpha-Synuclein at the Center of Disease Heterogeneity
title_full Beyond Strains: Molecular Diversity in Alpha-Synuclein at the Center of Disease Heterogeneity
title_fullStr Beyond Strains: Molecular Diversity in Alpha-Synuclein at the Center of Disease Heterogeneity
title_full_unstemmed Beyond Strains: Molecular Diversity in Alpha-Synuclein at the Center of Disease Heterogeneity
title_short Beyond Strains: Molecular Diversity in Alpha-Synuclein at the Center of Disease Heterogeneity
title_sort beyond strains: molecular diversity in alpha-synuclein at the center of disease heterogeneity
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10487421/
https://www.ncbi.nlm.nih.gov/pubmed/37686005
http://dx.doi.org/10.3390/ijms241713199
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