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Redefining the hypotheses driving Parkinson’s diseases research
Parkinson’s disease (PD) research has largely focused on the disease as a single entity centred on the development of neuronal pathology within the central nervous system. However, there is growing recognition that PD is not a single entity but instead reflects multiple diseases, in which different...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9018840/ https://www.ncbi.nlm.nih.gov/pubmed/35440633 http://dx.doi.org/10.1038/s41531-022-00307-w |
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author | Farrow, Sophie L. Cooper, Antony A. O’Sullivan, Justin M. |
author_facet | Farrow, Sophie L. Cooper, Antony A. O’Sullivan, Justin M. |
author_sort | Farrow, Sophie L. |
collection | PubMed |
description | Parkinson’s disease (PD) research has largely focused on the disease as a single entity centred on the development of neuronal pathology within the central nervous system. However, there is growing recognition that PD is not a single entity but instead reflects multiple diseases, in which different combinations of environmental, genetic and potential comorbid factors interact to direct individual disease trajectories. Moreover, an increasing body of recent research implicates peripheral tissues and non-neuronal cell types in the development of PD. These observations are consistent with the hypothesis that the initial causative changes for PD development need not occur in the central nervous system. Here, we discuss how the use of neuronal pathology as a shared, qualitative phenotype minimises insights into the possibility of multiple origins and aetiologies of PD. Furthermore, we discuss how considering PD as a single entity potentially impairs our understanding of the causative molecular mechanisms, approaches for patient stratification, identification of biomarkers, and the development of therapeutic approaches to PD. The clear consequence of there being distinct diseases that collectively form PD, is that there is no single biomarker or treatment for PD development or progression. We propose that diagnosis should shift away from the clinical definitions, towards biologically defined diseases that collectively form PD, to enable informative patient stratification. N-of-one type, clinical designs offer an unbiased, and agnostic approach to re-defining PD in terms of a group of many individual diseases. |
format | Online Article Text |
id | pubmed-9018840 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-90188402022-04-28 Redefining the hypotheses driving Parkinson’s diseases research Farrow, Sophie L. Cooper, Antony A. O’Sullivan, Justin M. NPJ Parkinsons Dis Perspective Parkinson’s disease (PD) research has largely focused on the disease as a single entity centred on the development of neuronal pathology within the central nervous system. However, there is growing recognition that PD is not a single entity but instead reflects multiple diseases, in which different combinations of environmental, genetic and potential comorbid factors interact to direct individual disease trajectories. Moreover, an increasing body of recent research implicates peripheral tissues and non-neuronal cell types in the development of PD. These observations are consistent with the hypothesis that the initial causative changes for PD development need not occur in the central nervous system. Here, we discuss how the use of neuronal pathology as a shared, qualitative phenotype minimises insights into the possibility of multiple origins and aetiologies of PD. Furthermore, we discuss how considering PD as a single entity potentially impairs our understanding of the causative molecular mechanisms, approaches for patient stratification, identification of biomarkers, and the development of therapeutic approaches to PD. The clear consequence of there being distinct diseases that collectively form PD, is that there is no single biomarker or treatment for PD development or progression. We propose that diagnosis should shift away from the clinical definitions, towards biologically defined diseases that collectively form PD, to enable informative patient stratification. N-of-one type, clinical designs offer an unbiased, and agnostic approach to re-defining PD in terms of a group of many individual diseases. Nature Publishing Group UK 2022-04-19 /pmc/articles/PMC9018840/ /pubmed/35440633 http://dx.doi.org/10.1038/s41531-022-00307-w Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Perspective Farrow, Sophie L. Cooper, Antony A. O’Sullivan, Justin M. Redefining the hypotheses driving Parkinson’s diseases research |
title | Redefining the hypotheses driving Parkinson’s diseases research |
title_full | Redefining the hypotheses driving Parkinson’s diseases research |
title_fullStr | Redefining the hypotheses driving Parkinson’s diseases research |
title_full_unstemmed | Redefining the hypotheses driving Parkinson’s diseases research |
title_short | Redefining the hypotheses driving Parkinson’s diseases research |
title_sort | redefining the hypotheses driving parkinson’s diseases research |
topic | Perspective |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9018840/ https://www.ncbi.nlm.nih.gov/pubmed/35440633 http://dx.doi.org/10.1038/s41531-022-00307-w |
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