Recent advances in targeting LRRK2 for Parkinson’s disease treatment
Abstract Parkinson’s disease (PD) is a neurodegenerative disease with severe movement problems. Current treatments mainly focus on symptom management by reducing dopaminergic pathways in the brain. Despite these therapies, ongoing disease progression undermines the effectiveness of prevalent approac...
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| Format: | Article |
| Language: | English |
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BMC
2025-07-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-025-06354-0 |
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| author | Mahsa Karami Pantea Majma Sanaye Atousa Ghorbani Roshanak Amirian Pouya Goleij Mehregan Babamohamadi Zhila Izadi |
| author_facet | Mahsa Karami Pantea Majma Sanaye Atousa Ghorbani Roshanak Amirian Pouya Goleij Mehregan Babamohamadi Zhila Izadi |
| author_sort | Mahsa Karami |
| collection | DOAJ |
| description | Abstract Parkinson’s disease (PD) is a neurodegenerative disease with severe movement problems. Current treatments mainly focus on symptom management by reducing dopaminergic pathways in the brain. Despite these therapies, ongoing disease progression undermines the effectiveness of prevalent approaches, necessitating exploring alternative methods anchored on genetic factors, notably the leucine-rich repeat kinase 2 (LRRK2) gene. Exploring LRRK2 gene pathogenesis has highlighted various mechanisms that may contribute to treating PD, including protein accumulation, altered cytoskeletal dynamics, neuro-inflammation, autophagy, and mitochondrial dysfunction. Based on the findings, there is an actual correlation between elevated levels of LRRK2 and the biomarkers and assays of PD. Furthermore, research results have suggested inhibiting LRRK2 as a therapeutic intervention targeting pathogenic mechanisms with varying degrees of efficacy. Our review wants to understand how LRRK2 works in the body and its relationship with the occurrence of PD by providing biochemical evidence, LRRK2 gene mutations and pathology, and the role of this gene in the immune system. We also discuss targeted therapies such as kinase inhibitors and Proteolysis targeting chimera and the application of using the LRRK2 protein to diagnose PD and develop bioassay designs. Finally, we mention the clinical trials conducted and the challenges and safety required. |
| format | Article |
| id | doaj-art-74d949daf6494de69dedf8518c74c82b |
| institution | Kabale University |
| issn | 1479-5876 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj-art-74d949daf6494de69dedf8518c74c82b2025-08-20T03:46:27ZengBMCJournal of Translational Medicine1479-58762025-07-0123112510.1186/s12967-025-06354-0Recent advances in targeting LRRK2 for Parkinson’s disease treatmentMahsa Karami0Pantea Majma Sanaye1Atousa Ghorbani2Roshanak Amirian3Pouya Goleij4Mehregan Babamohamadi5Zhila Izadi6Student Research Committee, Kermanshah University of Medical SciencesPharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical SciencesUSERN Office, Kermanshah University of Medical SciencesStudent Research Committee, Kermanshah University of Medical SciencesUSERN Office, Kermanshah University of Medical SciencesUSERN Office, Kermanshah University of Medical SciencesPharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical SciencesAbstract Parkinson’s disease (PD) is a neurodegenerative disease with severe movement problems. Current treatments mainly focus on symptom management by reducing dopaminergic pathways in the brain. Despite these therapies, ongoing disease progression undermines the effectiveness of prevalent approaches, necessitating exploring alternative methods anchored on genetic factors, notably the leucine-rich repeat kinase 2 (LRRK2) gene. Exploring LRRK2 gene pathogenesis has highlighted various mechanisms that may contribute to treating PD, including protein accumulation, altered cytoskeletal dynamics, neuro-inflammation, autophagy, and mitochondrial dysfunction. Based on the findings, there is an actual correlation between elevated levels of LRRK2 and the biomarkers and assays of PD. Furthermore, research results have suggested inhibiting LRRK2 as a therapeutic intervention targeting pathogenic mechanisms with varying degrees of efficacy. Our review wants to understand how LRRK2 works in the body and its relationship with the occurrence of PD by providing biochemical evidence, LRRK2 gene mutations and pathology, and the role of this gene in the immune system. We also discuss targeted therapies such as kinase inhibitors and Proteolysis targeting chimera and the application of using the LRRK2 protein to diagnose PD and develop bioassay designs. Finally, we mention the clinical trials conducted and the challenges and safety required.https://doi.org/10.1186/s12967-025-06354-0Parkinson’s diseaseLRRK2Neurodegenerative diseasesAutophagyPROTACMitochondrial dysfunction |
| spellingShingle | Mahsa Karami Pantea Majma Sanaye Atousa Ghorbani Roshanak Amirian Pouya Goleij Mehregan Babamohamadi Zhila Izadi Recent advances in targeting LRRK2 for Parkinson’s disease treatment Journal of Translational Medicine Parkinson’s disease LRRK2 Neurodegenerative diseases Autophagy PROTAC Mitochondrial dysfunction |
| title | Recent advances in targeting LRRK2 for Parkinson’s disease treatment |
| title_full | Recent advances in targeting LRRK2 for Parkinson’s disease treatment |
| title_fullStr | Recent advances in targeting LRRK2 for Parkinson’s disease treatment |
| title_full_unstemmed | Recent advances in targeting LRRK2 for Parkinson’s disease treatment |
| title_short | Recent advances in targeting LRRK2 for Parkinson’s disease treatment |
| title_sort | recent advances in targeting lrrk2 for parkinson s disease treatment |
| topic | Parkinson’s disease LRRK2 Neurodegenerative diseases Autophagy PROTAC Mitochondrial dysfunction |
| url | https://doi.org/10.1186/s12967-025-06354-0 |
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