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Mind the Gap: LRRK2 Phenotypes in the Clinic vs. in Patient Cells

Mutations in the Parkinson’s disease (PD) protein Leucine Rich Repeat Kinase 2 (LRRK2) have been under study for more than 15 years and our understanding of the cellular phenotypes for the pathogenic mutant forms of LRRK2 has significantly advanced. In parallel to research on LRRK2 mutations in expe...

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Autores principales: Goveas, Liesel, Mutez, Eugénie, Chartier-Harlin, Marie-Christine, Taymans, Jean-Marc
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145309/
https://www.ncbi.nlm.nih.gov/pubmed/33922322
http://dx.doi.org/10.3390/cells10050981
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author Goveas, Liesel
Mutez, Eugénie
Chartier-Harlin, Marie-Christine
Taymans, Jean-Marc
author_facet Goveas, Liesel
Mutez, Eugénie
Chartier-Harlin, Marie-Christine
Taymans, Jean-Marc
author_sort Goveas, Liesel
collection PubMed
description Mutations in the Parkinson’s disease (PD) protein Leucine Rich Repeat Kinase 2 (LRRK2) have been under study for more than 15 years and our understanding of the cellular phenotypes for the pathogenic mutant forms of LRRK2 has significantly advanced. In parallel to research on LRRK2 mutations in experimental systems, clinical characterization of patients carrying LRRK2 mutations has advanced, as has the analysis of cells that are derived from these patients, including fibroblasts, blood-derived cells, or cells rendered pluripotent. Under the hypothesis that patient clinical phenotypes are a consequence of a cascade of underlying molecular mechanisms gone astray, we currently have a unique opportunity to compare findings from patients and patient-derived cells to ask the question of whether the clinical phenotype of LRRK2 Parkinson’s disease and cellular phenotypes of LRRK2 patient-derived cells may be mutually informative. In this review, we aim to summarize the available information on phenotypes of LRRK2 mutations in the clinic, in patient-derived cells, and in experimental models in order to better understand the relationship between the three at the molecular and cellular levels and identify trends and gaps in correlating the data.
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spelling pubmed-81453092021-05-26 Mind the Gap: LRRK2 Phenotypes in the Clinic vs. in Patient Cells Goveas, Liesel Mutez, Eugénie Chartier-Harlin, Marie-Christine Taymans, Jean-Marc Cells Review Mutations in the Parkinson’s disease (PD) protein Leucine Rich Repeat Kinase 2 (LRRK2) have been under study for more than 15 years and our understanding of the cellular phenotypes for the pathogenic mutant forms of LRRK2 has significantly advanced. In parallel to research on LRRK2 mutations in experimental systems, clinical characterization of patients carrying LRRK2 mutations has advanced, as has the analysis of cells that are derived from these patients, including fibroblasts, blood-derived cells, or cells rendered pluripotent. Under the hypothesis that patient clinical phenotypes are a consequence of a cascade of underlying molecular mechanisms gone astray, we currently have a unique opportunity to compare findings from patients and patient-derived cells to ask the question of whether the clinical phenotype of LRRK2 Parkinson’s disease and cellular phenotypes of LRRK2 patient-derived cells may be mutually informative. In this review, we aim to summarize the available information on phenotypes of LRRK2 mutations in the clinic, in patient-derived cells, and in experimental models in order to better understand the relationship between the three at the molecular and cellular levels and identify trends and gaps in correlating the data. MDPI 2021-04-22 /pmc/articles/PMC8145309/ /pubmed/33922322 http://dx.doi.org/10.3390/cells10050981 Text en © 2021 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
Goveas, Liesel
Mutez, Eugénie
Chartier-Harlin, Marie-Christine
Taymans, Jean-Marc
Mind the Gap: LRRK2 Phenotypes in the Clinic vs. in Patient Cells
title Mind the Gap: LRRK2 Phenotypes in the Clinic vs. in Patient Cells
title_full Mind the Gap: LRRK2 Phenotypes in the Clinic vs. in Patient Cells
title_fullStr Mind the Gap: LRRK2 Phenotypes in the Clinic vs. in Patient Cells
title_full_unstemmed Mind the Gap: LRRK2 Phenotypes in the Clinic vs. in Patient Cells
title_short Mind the Gap: LRRK2 Phenotypes in the Clinic vs. in Patient Cells
title_sort mind the gap: lrrk2 phenotypes in the clinic vs. in patient cells
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145309/
https://www.ncbi.nlm.nih.gov/pubmed/33922322
http://dx.doi.org/10.3390/cells10050981
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