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Monogenetic Forms of Parkinson’s Disease – Bridging the Gap Between Genetics and Biomarkers

The therapy of neurodegenerative diseases such as Parkinson’s disease (PD) is still limited to the treatment of symptoms and primarily aimed at compensating for dopaminergic hypofunction. Numerous disease-modifying therapies currently in the pipeline attempt to modify the underlying pathomechanisms....

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Autores principales: Tönges, Lars, Kwon, Eun Hae, Klebe, Stephan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8934414/
https://www.ncbi.nlm.nih.gov/pubmed/35317530
http://dx.doi.org/10.3389/fnagi.2022.822949
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author Tönges, Lars
Kwon, Eun Hae
Klebe, Stephan
author_facet Tönges, Lars
Kwon, Eun Hae
Klebe, Stephan
author_sort Tönges, Lars
collection PubMed
description The therapy of neurodegenerative diseases such as Parkinson’s disease (PD) is still limited to the treatment of symptoms and primarily aimed at compensating for dopaminergic hypofunction. Numerous disease-modifying therapies currently in the pipeline attempt to modify the underlying pathomechanisms. In recent decades, the results of molecular genetics and biomarker research have raised hopes of earlier diagnosis and new neuroprotective therapeutic approaches. As the disease-causing processes in monogenetic forms of PD are better understood than in sporadic PD, these disease subsets are likely to benefit first from disease-modifying therapies. Recent studies have suggested that disease-relevant changes found in genetically linked forms of PD (i.e., PARK-LRRK2, PARK-GBA) can also be reproduced in patients in whom no genetic cause can be found, i.e., those with sporadic PD. It can, therefore, be assumed that as soon as the first causal therapy for genetic forms of PD is approved, more patients with PD will undergo genetic testing and counseling. Regarding future neuroprotective trials in neurodegenerative diseases and objective parameters such as biomarkers with high sensitivity and specificity for the diagnosis and course of the disease are needed. These biomarkers will also serve to monitor treatment success in clinical trials. Promising examples in PD, such as alpha-synuclein species, lysosomal enzymes, markers of amyloid and tau pathology, and neurofilament light chain, are under investigation in blood and CSF. This paper provides an overview of the opportunities and current limitations of monogenetic diagnostic and biomarker research in PD and aims to build a bridge between current knowledge and association with PD genetics and biomarkers.
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spelling pubmed-89344142022-03-21 Monogenetic Forms of Parkinson’s Disease – Bridging the Gap Between Genetics and Biomarkers Tönges, Lars Kwon, Eun Hae Klebe, Stephan Front Aging Neurosci Neuroscience The therapy of neurodegenerative diseases such as Parkinson’s disease (PD) is still limited to the treatment of symptoms and primarily aimed at compensating for dopaminergic hypofunction. Numerous disease-modifying therapies currently in the pipeline attempt to modify the underlying pathomechanisms. In recent decades, the results of molecular genetics and biomarker research have raised hopes of earlier diagnosis and new neuroprotective therapeutic approaches. As the disease-causing processes in monogenetic forms of PD are better understood than in sporadic PD, these disease subsets are likely to benefit first from disease-modifying therapies. Recent studies have suggested that disease-relevant changes found in genetically linked forms of PD (i.e., PARK-LRRK2, PARK-GBA) can also be reproduced in patients in whom no genetic cause can be found, i.e., those with sporadic PD. It can, therefore, be assumed that as soon as the first causal therapy for genetic forms of PD is approved, more patients with PD will undergo genetic testing and counseling. Regarding future neuroprotective trials in neurodegenerative diseases and objective parameters such as biomarkers with high sensitivity and specificity for the diagnosis and course of the disease are needed. These biomarkers will also serve to monitor treatment success in clinical trials. Promising examples in PD, such as alpha-synuclein species, lysosomal enzymes, markers of amyloid and tau pathology, and neurofilament light chain, are under investigation in blood and CSF. This paper provides an overview of the opportunities and current limitations of monogenetic diagnostic and biomarker research in PD and aims to build a bridge between current knowledge and association with PD genetics and biomarkers. Frontiers Media S.A. 2022-03-03 /pmc/articles/PMC8934414/ /pubmed/35317530 http://dx.doi.org/10.3389/fnagi.2022.822949 Text en Copyright © 2022 Tönges, Kwon and Klebe. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Tönges, Lars
Kwon, Eun Hae
Klebe, Stephan
Monogenetic Forms of Parkinson’s Disease – Bridging the Gap Between Genetics and Biomarkers
title Monogenetic Forms of Parkinson’s Disease – Bridging the Gap Between Genetics and Biomarkers
title_full Monogenetic Forms of Parkinson’s Disease – Bridging the Gap Between Genetics and Biomarkers
title_fullStr Monogenetic Forms of Parkinson’s Disease – Bridging the Gap Between Genetics and Biomarkers
title_full_unstemmed Monogenetic Forms of Parkinson’s Disease – Bridging the Gap Between Genetics and Biomarkers
title_short Monogenetic Forms of Parkinson’s Disease – Bridging the Gap Between Genetics and Biomarkers
title_sort monogenetic forms of parkinson’s disease – bridging the gap between genetics and biomarkers
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8934414/
https://www.ncbi.nlm.nih.gov/pubmed/35317530
http://dx.doi.org/10.3389/fnagi.2022.822949
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