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PARK7/DJ-1 in microglia: implications in Parkinson’s disease and relevance as a therapeutic target
Microglia are the immune effector cells of the brain playing critical roles in immune surveillance and neuroprotection in healthy conditions, while they can sustain neuroinflammatory and neurotoxic processes in neurodegenerative diseases, including Parkinson’s disease (PD). Although the precise trig...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10111685/ https://www.ncbi.nlm.nih.gov/pubmed/37072827 http://dx.doi.org/10.1186/s12974-023-02776-z |
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author | Lind-Holm Mogensen, Frida Scafidi, Andrea Poli, Aurélie Michelucci, Alessandro |
author_facet | Lind-Holm Mogensen, Frida Scafidi, Andrea Poli, Aurélie Michelucci, Alessandro |
author_sort | Lind-Holm Mogensen, Frida |
collection | PubMed |
description | Microglia are the immune effector cells of the brain playing critical roles in immune surveillance and neuroprotection in healthy conditions, while they can sustain neuroinflammatory and neurotoxic processes in neurodegenerative diseases, including Parkinson’s disease (PD). Although the precise triggers of PD remain obscure, causative genetic mutations, which aid in the identification of molecular pathways underlying the pathogenesis of idiopathic forms, represent 10% of the patients. Among the inherited forms, loss of function of PARK7, which encodes the protein DJ-1, results in autosomal recessive early-onset PD. Yet, although protection against oxidative stress is the most prominent task ascribed to DJ-1, the underlying mechanisms linking DJ-1 deficiency to the onset of PD are a current matter of investigation. This review provides an overview of the role of DJ-1 in neuroinflammation, with a special focus on its functions in microglia genetic programs and immunological traits. Furthermore, it discusses the relevance of targeting dysregulated pathways in microglia under DJ-1 deficiency and their importance as therapeutic targets in PD. Lastly, it addresses the prospect to consider DJ-1, detected in its oxidized form in idiopathic PD, as a biomarker and to take into account DJ-1-enhancing compounds as therapeutics dampening oxidative stress and neuroinflammation. |
format | Online Article Text |
id | pubmed-10111685 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-101116852023-04-19 PARK7/DJ-1 in microglia: implications in Parkinson’s disease and relevance as a therapeutic target Lind-Holm Mogensen, Frida Scafidi, Andrea Poli, Aurélie Michelucci, Alessandro J Neuroinflammation Review Microglia are the immune effector cells of the brain playing critical roles in immune surveillance and neuroprotection in healthy conditions, while they can sustain neuroinflammatory and neurotoxic processes in neurodegenerative diseases, including Parkinson’s disease (PD). Although the precise triggers of PD remain obscure, causative genetic mutations, which aid in the identification of molecular pathways underlying the pathogenesis of idiopathic forms, represent 10% of the patients. Among the inherited forms, loss of function of PARK7, which encodes the protein DJ-1, results in autosomal recessive early-onset PD. Yet, although protection against oxidative stress is the most prominent task ascribed to DJ-1, the underlying mechanisms linking DJ-1 deficiency to the onset of PD are a current matter of investigation. This review provides an overview of the role of DJ-1 in neuroinflammation, with a special focus on its functions in microglia genetic programs and immunological traits. Furthermore, it discusses the relevance of targeting dysregulated pathways in microglia under DJ-1 deficiency and their importance as therapeutic targets in PD. Lastly, it addresses the prospect to consider DJ-1, detected in its oxidized form in idiopathic PD, as a biomarker and to take into account DJ-1-enhancing compounds as therapeutics dampening oxidative stress and neuroinflammation. BioMed Central 2023-04-18 /pmc/articles/PMC10111685/ /pubmed/37072827 http://dx.doi.org/10.1186/s12974-023-02776-z 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/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Review Lind-Holm Mogensen, Frida Scafidi, Andrea Poli, Aurélie Michelucci, Alessandro PARK7/DJ-1 in microglia: implications in Parkinson’s disease and relevance as a therapeutic target |
title | PARK7/DJ-1 in microglia: implications in Parkinson’s disease and relevance as a therapeutic target |
title_full | PARK7/DJ-1 in microglia: implications in Parkinson’s disease and relevance as a therapeutic target |
title_fullStr | PARK7/DJ-1 in microglia: implications in Parkinson’s disease and relevance as a therapeutic target |
title_full_unstemmed | PARK7/DJ-1 in microglia: implications in Parkinson’s disease and relevance as a therapeutic target |
title_short | PARK7/DJ-1 in microglia: implications in Parkinson’s disease and relevance as a therapeutic target |
title_sort | park7/dj-1 in microglia: implications in parkinson’s disease and relevance as a therapeutic target |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10111685/ https://www.ncbi.nlm.nih.gov/pubmed/37072827 http://dx.doi.org/10.1186/s12974-023-02776-z |
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