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Multiple-Hit Hypothesis in Parkinson’s Disease: LRRK2 and Inflammation
The multiple hit hypothesis for Parkinson’s disease (PD) suggests that an interaction between multiple (genetic and/or environmental) risk factors is needed to trigger the pathology. Leucine-Rich Repeat Kinase 2 (LRRK2) is an interesting protein to study in this context and is the focus of this revi...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7199384/ https://www.ncbi.nlm.nih.gov/pubmed/32410948 http://dx.doi.org/10.3389/fnins.2020.00376 |
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author | Cabezudo, Diego Baekelandt, Veerle Lobbestael, Evy |
author_facet | Cabezudo, Diego Baekelandt, Veerle Lobbestael, Evy |
author_sort | Cabezudo, Diego |
collection | PubMed |
description | The multiple hit hypothesis for Parkinson’s disease (PD) suggests that an interaction between multiple (genetic and/or environmental) risk factors is needed to trigger the pathology. Leucine-Rich Repeat Kinase 2 (LRRK2) is an interesting protein to study in this context and is the focus of this review. More than 15 years of intensive research have identified several cellular pathways in which LRRK2 is involved, yet its exact physiological role or contribution to PD is not completely understood. Pathogenic mutations in LRRK2 are the most common genetic cause of PD but most likely require additional triggers to develop PD, as suggested by the reduced penetrance of the LRRK2 G2019S mutation. LRRK2 expression is high in immune cells such as monocytes, neutrophils, or dendritic cells, compared to neurons or glial cells and evidence for a role of LRRK2 in the immune system is emerging. This has led to the hypothesis that an inflammatory trigger is needed for pathogenic LRRK2 mutations to induce a PD phenotype. In this review, we will discuss the link between LRRK2 and inflammation and how this could play an active role in PD etiology. |
format | Online Article Text |
id | pubmed-7199384 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-71993842020-05-14 Multiple-Hit Hypothesis in Parkinson’s Disease: LRRK2 and Inflammation Cabezudo, Diego Baekelandt, Veerle Lobbestael, Evy Front Neurosci Neuroscience The multiple hit hypothesis for Parkinson’s disease (PD) suggests that an interaction between multiple (genetic and/or environmental) risk factors is needed to trigger the pathology. Leucine-Rich Repeat Kinase 2 (LRRK2) is an interesting protein to study in this context and is the focus of this review. More than 15 years of intensive research have identified several cellular pathways in which LRRK2 is involved, yet its exact physiological role or contribution to PD is not completely understood. Pathogenic mutations in LRRK2 are the most common genetic cause of PD but most likely require additional triggers to develop PD, as suggested by the reduced penetrance of the LRRK2 G2019S mutation. LRRK2 expression is high in immune cells such as monocytes, neutrophils, or dendritic cells, compared to neurons or glial cells and evidence for a role of LRRK2 in the immune system is emerging. This has led to the hypothesis that an inflammatory trigger is needed for pathogenic LRRK2 mutations to induce a PD phenotype. In this review, we will discuss the link between LRRK2 and inflammation and how this could play an active role in PD etiology. Frontiers Media S.A. 2020-04-28 /pmc/articles/PMC7199384/ /pubmed/32410948 http://dx.doi.org/10.3389/fnins.2020.00376 Text en Copyright © 2020 Cabezudo, Baekelandt and Lobbestael. 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) 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 Cabezudo, Diego Baekelandt, Veerle Lobbestael, Evy Multiple-Hit Hypothesis in Parkinson’s Disease: LRRK2 and Inflammation |
title | Multiple-Hit Hypothesis in Parkinson’s Disease: LRRK2 and Inflammation |
title_full | Multiple-Hit Hypothesis in Parkinson’s Disease: LRRK2 and Inflammation |
title_fullStr | Multiple-Hit Hypothesis in Parkinson’s Disease: LRRK2 and Inflammation |
title_full_unstemmed | Multiple-Hit Hypothesis in Parkinson’s Disease: LRRK2 and Inflammation |
title_short | Multiple-Hit Hypothesis in Parkinson’s Disease: LRRK2 and Inflammation |
title_sort | multiple-hit hypothesis in parkinson’s disease: lrrk2 and inflammation |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7199384/ https://www.ncbi.nlm.nih.gov/pubmed/32410948 http://dx.doi.org/10.3389/fnins.2020.00376 |
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