Roles of LRRK2 and its orthologs in protecting against neurodegeneration and neurodevelopmental defects
In humans, variants in the LRRK2 gene are the most prevalent risk factors for Parkinson’s disease (PD). Whereas studies in model organisms have long indicated that the orthologs of the wild-type LRRK proteins protect against neurodegeneration, newer findings indicate that they also protect against n...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2025-04-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2025.1569733/full |
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| author | An Phu Tran Nguyen Linh Thi Nhat Nguyen Bailey A. Stokke Christopher C. Quinn |
| author_facet | An Phu Tran Nguyen Linh Thi Nhat Nguyen Bailey A. Stokke Christopher C. Quinn |
| author_sort | An Phu Tran Nguyen |
| collection | DOAJ |
| description | In humans, variants in the LRRK2 gene are the most prevalent risk factors for Parkinson’s disease (PD). Whereas studies in model organisms have long indicated that the orthologs of the wild-type LRRK proteins protect against neurodegeneration, newer findings indicate that they also protect against neurodevelopmental defects. This normal role of the LRRK proteins can be disrupted by either gain-of-function (GOF) or loss-of-function (LOF) mutations, leading to neurodegeneration and neurodevelopmental defects. Here, we review the roles of the LRRK proteins and their orthologs in these processes, with a focus on autophagy as a common factor that may mediate both of these roles. We also highlight the potential for experiments in vertebrate and invertebrate model systems to synergistically inform our understanding of the role of LRRK proteins in protecting against neurological disorders. |
| format | Article |
| id | doaj-art-ab9947ed8ff048c3b8c1a8a92ae98b02 |
| institution | OA Journals |
| issn | 2296-634X |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj-art-ab9947ed8ff048c3b8c1a8a92ae98b022025-08-20T01:47:55ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2025-04-011310.3389/fcell.2025.15697331569733Roles of LRRK2 and its orthologs in protecting against neurodegeneration and neurodevelopmental defectsAn Phu Tran NguyenLinh Thi Nhat NguyenBailey A. StokkeChristopher C. QuinnIn humans, variants in the LRRK2 gene are the most prevalent risk factors for Parkinson’s disease (PD). Whereas studies in model organisms have long indicated that the orthologs of the wild-type LRRK proteins protect against neurodegeneration, newer findings indicate that they also protect against neurodevelopmental defects. This normal role of the LRRK proteins can be disrupted by either gain-of-function (GOF) or loss-of-function (LOF) mutations, leading to neurodegeneration and neurodevelopmental defects. Here, we review the roles of the LRRK proteins and their orthologs in these processes, with a focus on autophagy as a common factor that may mediate both of these roles. We also highlight the potential for experiments in vertebrate and invertebrate model systems to synergistically inform our understanding of the role of LRRK proteins in protecting against neurological disorders.https://www.frontiersin.org/articles/10.3389/fcell.2025.1569733/fullLRRK2Parkinson’s diseaseautismintellectual disabilityneurodegeneration |
| spellingShingle | An Phu Tran Nguyen Linh Thi Nhat Nguyen Bailey A. Stokke Christopher C. Quinn Roles of LRRK2 and its orthologs in protecting against neurodegeneration and neurodevelopmental defects Frontiers in Cell and Developmental Biology LRRK2 Parkinson’s disease autism intellectual disability neurodegeneration |
| title | Roles of LRRK2 and its orthologs in protecting against neurodegeneration and neurodevelopmental defects |
| title_full | Roles of LRRK2 and its orthologs in protecting against neurodegeneration and neurodevelopmental defects |
| title_fullStr | Roles of LRRK2 and its orthologs in protecting against neurodegeneration and neurodevelopmental defects |
| title_full_unstemmed | Roles of LRRK2 and its orthologs in protecting against neurodegeneration and neurodevelopmental defects |
| title_short | Roles of LRRK2 and its orthologs in protecting against neurodegeneration and neurodevelopmental defects |
| title_sort | roles of lrrk2 and its orthologs in protecting against neurodegeneration and neurodevelopmental defects |
| topic | LRRK2 Parkinson’s disease autism intellectual disability neurodegeneration |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2025.1569733/full |
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