The Double-Faceted Role of Leucine-Rich Repeat Kinase 2 in the Immunopathogenesis of Parkinson’s Disease
Leucine-rich repeat kinase 2 (LRRK2) is one of the most common causative genes in Parkinson’s disease (PD). The complex structure of this multiple domains’ protein determines its versatile functions in multiple physiological processes, including migration, autophagy, phagocytosis, and mitochondrial...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Aging Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2022.909303/full |
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| author | Mengfei Zhang Mengfei Zhang Mengfei Zhang Chaoyi Li Chaoyi Li Chaoyi Li Jie Ren Jie Ren Jie Ren Huakun Wang Huakun Wang Huakun Wang Fang Yi Fang Yi Fang Yi Junjiao Wu Junjiao Wu Junjiao Wu Yu Tang Yu Tang Yu Tang Yu Tang |
| author_facet | Mengfei Zhang Mengfei Zhang Mengfei Zhang Chaoyi Li Chaoyi Li Chaoyi Li Jie Ren Jie Ren Jie Ren Huakun Wang Huakun Wang Huakun Wang Fang Yi Fang Yi Fang Yi Junjiao Wu Junjiao Wu Junjiao Wu Yu Tang Yu Tang Yu Tang Yu Tang |
| author_sort | Mengfei Zhang |
| collection | DOAJ |
| description | Leucine-rich repeat kinase 2 (LRRK2) is one of the most common causative genes in Parkinson’s disease (PD). The complex structure of this multiple domains’ protein determines its versatile functions in multiple physiological processes, including migration, autophagy, phagocytosis, and mitochondrial function, among others. Mounting studies have also demonstrated the role of LRRK2 in mediating neuroinflammation, the prominent hallmark of PD, and intricate functions in immune cells, such as microglia, macrophages, and astrocytes. Of those, microglia were extensively studied in PD, which serves as the resident immune cell of the central nervous system that is rapidly activated upon neuronal injury and pathogenic insult. Moreover, the activation and function of immune cells can be achieved by modulating their intracellular metabolic profiles, in which LRRK2 plays an emerging role. Here, we provide an updated review focusing on the double-faceted role of LRRK2 in regulating various cellular physiology and immune functions especially in microglia. Moreover, we will summarize the latest discovery of the three-dimensional structure of LRRK2, as well as the function and dysfunction of LRRK2 in immune cell-related pathways. |
| first_indexed | 2024-04-13T08:27:55Z |
| format | Article |
| id | doaj.art-6166fa66ee9b419eb12f1eb02fbd0cf3 |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-04-13T08:27:55Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-6166fa66ee9b419eb12f1eb02fbd0cf32022-12-22T02:54:22ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652022-05-011410.3389/fnagi.2022.909303909303The Double-Faceted Role of Leucine-Rich Repeat Kinase 2 in the Immunopathogenesis of Parkinson’s DiseaseMengfei Zhang0Mengfei Zhang1Mengfei Zhang2Chaoyi Li3Chaoyi Li4Chaoyi Li5Jie Ren6Jie Ren7Jie Ren8Huakun Wang9Huakun Wang10Huakun Wang11Fang Yi12Fang Yi13Fang Yi14Junjiao Wu15Junjiao Wu16Junjiao Wu17Yu Tang18Yu Tang19Yu Tang20Yu Tang21Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, ChinaAging Research Center, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Geriatrics, Xiangya Hospital, Central South University, Changsha, ChinaAging Research Center, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Geriatrics, Xiangya Hospital, Central South University, Changsha, ChinaAging Research Center, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Geriatrics, Xiangya Hospital, Central South University, Changsha, ChinaAging Research Center, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Geriatrics, Xiangya Hospital, Central South University, Changsha, ChinaAging Research Center, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Rheumatology and Immunology, Xiangya Hospital, Central South University, Changsha, ChinaProvincial Clinical Research Center for Rheumatic and Immunologic Diseases, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Geriatrics, Xiangya Hospital, Central South University, Changsha, ChinaAging Research Center, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, ChinaLeucine-rich repeat kinase 2 (LRRK2) is one of the most common causative genes in Parkinson’s disease (PD). The complex structure of this multiple domains’ protein determines its versatile functions in multiple physiological processes, including migration, autophagy, phagocytosis, and mitochondrial function, among others. Mounting studies have also demonstrated the role of LRRK2 in mediating neuroinflammation, the prominent hallmark of PD, and intricate functions in immune cells, such as microglia, macrophages, and astrocytes. Of those, microglia were extensively studied in PD, which serves as the resident immune cell of the central nervous system that is rapidly activated upon neuronal injury and pathogenic insult. Moreover, the activation and function of immune cells can be achieved by modulating their intracellular metabolic profiles, in which LRRK2 plays an emerging role. Here, we provide an updated review focusing on the double-faceted role of LRRK2 in regulating various cellular physiology and immune functions especially in microglia. Moreover, we will summarize the latest discovery of the three-dimensional structure of LRRK2, as well as the function and dysfunction of LRRK2 in immune cell-related pathways.https://www.frontiersin.org/articles/10.3389/fnagi.2022.909303/fullParkinson’s diseaseLRRK2neuroinflammationmicrogliaimmune function |
| spellingShingle | Mengfei Zhang Mengfei Zhang Mengfei Zhang Chaoyi Li Chaoyi Li Chaoyi Li Jie Ren Jie Ren Jie Ren Huakun Wang Huakun Wang Huakun Wang Fang Yi Fang Yi Fang Yi Junjiao Wu Junjiao Wu Junjiao Wu Yu Tang Yu Tang Yu Tang Yu Tang The Double-Faceted Role of Leucine-Rich Repeat Kinase 2 in the Immunopathogenesis of Parkinson’s Disease Frontiers in Aging Neuroscience Parkinson’s disease LRRK2 neuroinflammation microglia immune function |
| title | The Double-Faceted Role of Leucine-Rich Repeat Kinase 2 in the Immunopathogenesis of Parkinson’s Disease |
| title_full | The Double-Faceted Role of Leucine-Rich Repeat Kinase 2 in the Immunopathogenesis of Parkinson’s Disease |
| title_fullStr | The Double-Faceted Role of Leucine-Rich Repeat Kinase 2 in the Immunopathogenesis of Parkinson’s Disease |
| title_full_unstemmed | The Double-Faceted Role of Leucine-Rich Repeat Kinase 2 in the Immunopathogenesis of Parkinson’s Disease |
| title_short | The Double-Faceted Role of Leucine-Rich Repeat Kinase 2 in the Immunopathogenesis of Parkinson’s Disease |
| title_sort | double faceted role of leucine rich repeat kinase 2 in the immunopathogenesis of parkinson s disease |
| topic | Parkinson’s disease LRRK2 neuroinflammation microglia immune function |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2022.909303/full |
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