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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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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. |
format | Online Article Text |
id | pubmed-10487421 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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