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Phosphatases of α-synuclein, LRRK2, and tau: important players in the phosphorylation-dependent pathology of Parkinsonism
An important challenge in the field of Parkinson’s disease (PD) is to develop disease modifying therapies capable of stalling or even halting disease progression. Coupled to this challenge is the need to identify disease biomarkers, in order to identify pre-symptomatic hallmarks of disease and monit...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2014
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4224088/ https://www.ncbi.nlm.nih.gov/pubmed/25426138 http://dx.doi.org/10.3389/fgene.2014.00382 |
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author | Taymans, Jean-Marc Baekelandt, Veerle |
author_facet | Taymans, Jean-Marc Baekelandt, Veerle |
author_sort | Taymans, Jean-Marc |
collection | PubMed |
description | An important challenge in the field of Parkinson’s disease (PD) is to develop disease modifying therapies capable of stalling or even halting disease progression. Coupled to this challenge is the need to identify disease biomarkers, in order to identify pre-symptomatic hallmarks of disease and monitor disease progression. The answer to these challenges lies in the elucidation of the molecular causes underlying PD, for which important leads are disease genes identified in studies investigating the underlying genetic causes of PD. LRRK2 and α-syn have been both linked to familial forms of PD as well as associated to sporadic PD. Another gene, microtubule associated protein tau (MAPT), has been genetically linked to a dominant form of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) and genome-wide association studies report a strong association between MAPT and sporadic PD. Interestingly, LRRK2, α-syn, and tau are all phosphorylated proteins, and their phosphorylation patterns are linked to disease. In this review, we provide an overview of the evidence linking LRRK2, α-syn, and tau phosphorylation to PD pathology and focus on studies which have identified phosphatases responsible for dephosphorylation of pathology-related phosphorylations. We also discuss how the LRRK2, α-syn, and tau phosphatases may point to separate or cross-talking pathological pathways in PD. Finally, we will discuss how the study of phosphatases of dominant Parkinsonism proteins opens perspectives for targeting pathological phosphorylation events. |
format | Online Article Text |
id | pubmed-4224088 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-42240882014-11-25 Phosphatases of α-synuclein, LRRK2, and tau: important players in the phosphorylation-dependent pathology of Parkinsonism Taymans, Jean-Marc Baekelandt, Veerle Front Genet Genetics An important challenge in the field of Parkinson’s disease (PD) is to develop disease modifying therapies capable of stalling or even halting disease progression. Coupled to this challenge is the need to identify disease biomarkers, in order to identify pre-symptomatic hallmarks of disease and monitor disease progression. The answer to these challenges lies in the elucidation of the molecular causes underlying PD, for which important leads are disease genes identified in studies investigating the underlying genetic causes of PD. LRRK2 and α-syn have been both linked to familial forms of PD as well as associated to sporadic PD. Another gene, microtubule associated protein tau (MAPT), has been genetically linked to a dominant form of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) and genome-wide association studies report a strong association between MAPT and sporadic PD. Interestingly, LRRK2, α-syn, and tau are all phosphorylated proteins, and their phosphorylation patterns are linked to disease. In this review, we provide an overview of the evidence linking LRRK2, α-syn, and tau phosphorylation to PD pathology and focus on studies which have identified phosphatases responsible for dephosphorylation of pathology-related phosphorylations. We also discuss how the LRRK2, α-syn, and tau phosphatases may point to separate or cross-talking pathological pathways in PD. Finally, we will discuss how the study of phosphatases of dominant Parkinsonism proteins opens perspectives for targeting pathological phosphorylation events. Frontiers Media S.A. 2014-11-07 /pmc/articles/PMC4224088/ /pubmed/25426138 http://dx.doi.org/10.3389/fgene.2014.00382 Text en Copyright © 2014 Taymans and Baekelandt. http://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) or licensor 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 | Genetics Taymans, Jean-Marc Baekelandt, Veerle Phosphatases of α-synuclein, LRRK2, and tau: important players in the phosphorylation-dependent pathology of Parkinsonism |
title | Phosphatases of α-synuclein, LRRK2, and tau: important players in the phosphorylation-dependent pathology of Parkinsonism |
title_full | Phosphatases of α-synuclein, LRRK2, and tau: important players in the phosphorylation-dependent pathology of Parkinsonism |
title_fullStr | Phosphatases of α-synuclein, LRRK2, and tau: important players in the phosphorylation-dependent pathology of Parkinsonism |
title_full_unstemmed | Phosphatases of α-synuclein, LRRK2, and tau: important players in the phosphorylation-dependent pathology of Parkinsonism |
title_short | Phosphatases of α-synuclein, LRRK2, and tau: important players in the phosphorylation-dependent pathology of Parkinsonism |
title_sort | phosphatases of α-synuclein, lrrk2, and tau: important players in the phosphorylation-dependent pathology of parkinsonism |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4224088/ https://www.ncbi.nlm.nih.gov/pubmed/25426138 http://dx.doi.org/10.3389/fgene.2014.00382 |
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