Targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) to tackle central nervous system diseases: role as a promising approach
Abstract Atherosclerosis-associated disease (ASD) represents a complex pathological condition, characterized by the formation of atherosclerotic plaques within the arterial walls, encompassing cholesterol depositions, which is primarily attributed to elevated levels of low-density lipoprotein-choles...
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BMC
2025-07-01
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| Series: | European Journal of Medical Research |
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| Online Access: | https://doi.org/10.1186/s40001-025-02937-1 |
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| author | Xiaoxiao Zheng Wei Yuan Ling Li Hongyue Ma Mingxia Zhu Xiuli Li Xinhong Feng |
| author_facet | Xiaoxiao Zheng Wei Yuan Ling Li Hongyue Ma Mingxia Zhu Xiuli Li Xinhong Feng |
| author_sort | Xiaoxiao Zheng |
| collection | DOAJ |
| description | Abstract Atherosclerosis-associated disease (ASD) represents a complex pathological condition, characterized by the formation of atherosclerotic plaques within the arterial walls, encompassing cholesterol depositions, which is primarily attributed to elevated levels of low-density lipoprotein-cholesterol (LDL-C). A log-linear association between the absolute magnitude of LDL-C exposure and ASD risk has been widely studied. High levels of LDL-C have been acknowledged as the predominant culprit. The previous research findings have demonstrated that PCSK9 inhibitors (PCSK9i) can remarkably diminish the risk of ASD. The current research has primarily focused on the relevance of PCSK9 to the cardiovascular system and lipid metabolism; however, an increasing body of evidence shows that PCSK9 is pivotal in pathogenic processes in other organ systems. Yet, PCSK9’s impact on the brain is complex and not fully clarified, although several recent studies emphasize a putative role of its impact on various neurodegenerative disorders. Among neurological disorders, not only stroke but neurogenesis, neural cell differentiation, central LDL receptor metabolism, neural cell apoptosis, neuroinflammation, alcohol use disorder (AUD), amyotrophic lateral sclerosis(ALS), and Alzheimer’s Disease (AD) are related to PCSK9. PCSK9 expression in brain is low but greatly upregulated in neurological disorders. Therefore, PCSK9 is a promising pathway for the treatment of central nervous diseases. This review comprehensively describes evidence from the previous research on the effects of PCSK9i on the central nervous system, with a focus on the clinical potential of PCSK9i. We anticipate that this review will generate data that will help biomedical researchers or clinical workers develop treatments for the neurological diseases based on PCSK9i. |
| format | Article |
| id | doaj-art-b8227e0cf2b44dca835766d185cae4f7 |
| institution | Kabale University |
| issn | 2047-783X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | European Journal of Medical Research |
| spelling | doaj-art-b8227e0cf2b44dca835766d185cae4f72025-08-20T03:42:44ZengBMCEuropean Journal of Medical Research2047-783X2025-07-0130111910.1186/s40001-025-02937-1Targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) to tackle central nervous system diseases: role as a promising approachXiaoxiao Zheng0Wei Yuan1Ling Li2Hongyue Ma3Mingxia Zhu4Xiuli Li5Xinhong Feng6Department of Neurology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine, Tsinghua UniversityDepartment of Orthopedics, Fuxing Hospital, Capital Medical UniversityDepartment of Neurology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine, Tsinghua UniversityDepartment of Neurology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine, Tsinghua UniversityDepartment of Neurology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine, Tsinghua UniversityDepartment of Neurology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine, Tsinghua UniversityDepartment of Neurology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine, Tsinghua UniversityAbstract Atherosclerosis-associated disease (ASD) represents a complex pathological condition, characterized by the formation of atherosclerotic plaques within the arterial walls, encompassing cholesterol depositions, which is primarily attributed to elevated levels of low-density lipoprotein-cholesterol (LDL-C). A log-linear association between the absolute magnitude of LDL-C exposure and ASD risk has been widely studied. High levels of LDL-C have been acknowledged as the predominant culprit. The previous research findings have demonstrated that PCSK9 inhibitors (PCSK9i) can remarkably diminish the risk of ASD. The current research has primarily focused on the relevance of PCSK9 to the cardiovascular system and lipid metabolism; however, an increasing body of evidence shows that PCSK9 is pivotal in pathogenic processes in other organ systems. Yet, PCSK9’s impact on the brain is complex and not fully clarified, although several recent studies emphasize a putative role of its impact on various neurodegenerative disorders. Among neurological disorders, not only stroke but neurogenesis, neural cell differentiation, central LDL receptor metabolism, neural cell apoptosis, neuroinflammation, alcohol use disorder (AUD), amyotrophic lateral sclerosis(ALS), and Alzheimer’s Disease (AD) are related to PCSK9. PCSK9 expression in brain is low but greatly upregulated in neurological disorders. Therefore, PCSK9 is a promising pathway for the treatment of central nervous diseases. This review comprehensively describes evidence from the previous research on the effects of PCSK9i on the central nervous system, with a focus on the clinical potential of PCSK9i. We anticipate that this review will generate data that will help biomedical researchers or clinical workers develop treatments for the neurological diseases based on PCSK9i.https://doi.org/10.1186/s40001-025-02937-1PCSK9PCSK9 inhibitorsLDLCentral nervous system diseasesAtherosclerosis |
| spellingShingle | Xiaoxiao Zheng Wei Yuan Ling Li Hongyue Ma Mingxia Zhu Xiuli Li Xinhong Feng Targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) to tackle central nervous system diseases: role as a promising approach European Journal of Medical Research PCSK9 PCSK9 inhibitors LDL Central nervous system diseases Atherosclerosis |
| title | Targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) to tackle central nervous system diseases: role as a promising approach |
| title_full | Targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) to tackle central nervous system diseases: role as a promising approach |
| title_fullStr | Targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) to tackle central nervous system diseases: role as a promising approach |
| title_full_unstemmed | Targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) to tackle central nervous system diseases: role as a promising approach |
| title_short | Targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) to tackle central nervous system diseases: role as a promising approach |
| title_sort | targeting proprotein convertase subtilisin kexin type 9 pcsk9 to tackle central nervous system diseases role as a promising approach |
| topic | PCSK9 PCSK9 inhibitors LDL Central nervous system diseases Atherosclerosis |
| url | https://doi.org/10.1186/s40001-025-02937-1 |
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