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The heterogeneity of Parkinson’s disease

The heterogeneity of Parkinson’s disease (PD), i.e. the various clinical phenotypes, pathological findings, genetic predispositions and probably also the various implicated pathophysiological pathways pose a major challenge for future research projects and therapeutic trail design. We outline severa...

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Autores principales: Wüllner, Ullrich, Borghammer, Per, Choe, Chi-un, Csoti, Ilona, Falkenburger, Björn, Gasser, Thomas, Lingor, Paul, Riederer, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Vienna 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10174621/
https://www.ncbi.nlm.nih.gov/pubmed/37169935
http://dx.doi.org/10.1007/s00702-023-02635-4
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author Wüllner, Ullrich
Borghammer, Per
Choe, Chi-un
Csoti, Ilona
Falkenburger, Björn
Gasser, Thomas
Lingor, Paul
Riederer, Peter
author_facet Wüllner, Ullrich
Borghammer, Per
Choe, Chi-un
Csoti, Ilona
Falkenburger, Björn
Gasser, Thomas
Lingor, Paul
Riederer, Peter
author_sort Wüllner, Ullrich
collection PubMed
description The heterogeneity of Parkinson’s disease (PD), i.e. the various clinical phenotypes, pathological findings, genetic predispositions and probably also the various implicated pathophysiological pathways pose a major challenge for future research projects and therapeutic trail design. We outline several pathophysiological concepts, pathways and mechanisms, including the presumed roles of α-synuclein misfolding and aggregation, Lewy bodies, oxidative stress, iron and melanin, deficient autophagy processes, insulin and incretin signaling, T-cell autoimmunity, the gut–brain axis and the evidence that microbial (viral) agents may induce molecular hallmarks of neurodegeneration. The hypothesis is discussed, whether PD might indeed be triggered by exogenous (infectious) agents in susceptible individuals upon entry via the olfactory bulb (brain first) or the gut (body-first), which would support the idea that disease mechanisms may change over time. The unresolved heterogeneity of PD may have contributed to the failure of past clinical trials, which attempted to slow the course of PD. We thus conclude that PD patients need personalized therapeutic approaches tailored to specific phenomenological and etiologic subtypes of disease.
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spelling pubmed-101746212023-05-14 The heterogeneity of Parkinson’s disease Wüllner, Ullrich Borghammer, Per Choe, Chi-un Csoti, Ilona Falkenburger, Björn Gasser, Thomas Lingor, Paul Riederer, Peter J Neural Transm (Vienna) Neurology and Preclinical Neurological Studies - Review Article The heterogeneity of Parkinson’s disease (PD), i.e. the various clinical phenotypes, pathological findings, genetic predispositions and probably also the various implicated pathophysiological pathways pose a major challenge for future research projects and therapeutic trail design. We outline several pathophysiological concepts, pathways and mechanisms, including the presumed roles of α-synuclein misfolding and aggregation, Lewy bodies, oxidative stress, iron and melanin, deficient autophagy processes, insulin and incretin signaling, T-cell autoimmunity, the gut–brain axis and the evidence that microbial (viral) agents may induce molecular hallmarks of neurodegeneration. The hypothesis is discussed, whether PD might indeed be triggered by exogenous (infectious) agents in susceptible individuals upon entry via the olfactory bulb (brain first) or the gut (body-first), which would support the idea that disease mechanisms may change over time. The unresolved heterogeneity of PD may have contributed to the failure of past clinical trials, which attempted to slow the course of PD. We thus conclude that PD patients need personalized therapeutic approaches tailored to specific phenomenological and etiologic subtypes of disease. Springer Vienna 2023-05-11 2023 /pmc/articles/PMC10174621/ /pubmed/37169935 http://dx.doi.org/10.1007/s00702-023-02635-4 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Neurology and Preclinical Neurological Studies - Review Article
Wüllner, Ullrich
Borghammer, Per
Choe, Chi-un
Csoti, Ilona
Falkenburger, Björn
Gasser, Thomas
Lingor, Paul
Riederer, Peter
The heterogeneity of Parkinson’s disease
title The heterogeneity of Parkinson’s disease
title_full The heterogeneity of Parkinson’s disease
title_fullStr The heterogeneity of Parkinson’s disease
title_full_unstemmed The heterogeneity of Parkinson’s disease
title_short The heterogeneity of Parkinson’s disease
title_sort heterogeneity of parkinson’s disease
topic Neurology and Preclinical Neurological Studies - Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10174621/
https://www.ncbi.nlm.nih.gov/pubmed/37169935
http://dx.doi.org/10.1007/s00702-023-02635-4
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