Therapeutic potential of Simvastatin in ALS: Enhanced axonal integrity and motor neuron survival through Apoa4 and Alb modulation
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the selective death of motor neurons in the spinal cord, brainstem, and motor cortex. This study investigates the effects of simvastatin on the G93A-copper/zinc superoxide dismutase (G93ASOD1) transgenic mouse model...
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Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina
2024-11-01
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| Series: | Biomolecules & Biomedicine |
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| Online Access: | https://www.bjbms.org/ojs/index.php/bjbms/article/view/11218 |
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| author | Song Luo Xiaorui Wang Bo Ma Dongliang Liu Li Li Lijin Wang Ning Ding Liangyu Zou Jie Wang Jialin Pan Daoqian Sang Huadong Zhou Hongdang Qu Yi Lu Lijuan Yang |
| author_facet | Song Luo Xiaorui Wang Bo Ma Dongliang Liu Li Li Lijin Wang Ning Ding Liangyu Zou Jie Wang Jialin Pan Daoqian Sang Huadong Zhou Hongdang Qu Yi Lu Lijuan Yang |
| author_sort | Song Luo |
| collection | DOAJ |
| description | Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the selective death of motor neurons in the spinal cord, brainstem, and motor cortex. This study investigates the effects of simvastatin on the G93A-copper/zinc superoxide dismutase (G93ASOD1) transgenic mouse model of ALS. The experiment included three groups: C57BL/6 wild-type (WT) mice, C57BL/6J SOD1G93A mice treated with PBS (SOD1G93A + PBS), and C57BL/6J SOD1G93A mice treated with simvastatin (SOD1G93A + simvastatin). The primary endpoints were survival rates, body weight changes, performance in pole climbing and suspension tests, and neurological deficit scores. Pathological changes were assessed using H&E staining, transmission electron microscopy, Nissl staining, and Masson staining. Proteomic and metabolomic analyses were performed to identify differentially expressed proteins (DEPs) and metabolites. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were used to measure gene expression. Although there were no significant differences in survival rates, body weight, pole climbing, and suspension test performance, or neurological deficit scores between the SOD1G93A + simvastatin and SOD1G93A + PBS groups, simvastatin treatment improved axonal organization within the spinal cord, increased the number of neurons, and reduced cytoplasmic swelling and gastrocnemius fibrosis. A total of 47 DEPs and 13 differential metabolites were identified between the SOD1G93A + PBS and SOD1G93A + simvastatin groups. Notably, the expression levels of Apoa4 and Alb were elevated in the SOD1G93A + simvastatin group compared to the SOD1G93A + PBS group. Our results suggest that simvastatin may have potential therapeutic effects in ALS, likely involving the modulation of Apoa4 and Alb expression.
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| format | Article |
| id | doaj-art-e65bcf1bf9f54400a645f70da5ade889 |
| institution | OA Journals |
| issn | 2831-0896 2831-090X |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina |
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| series | Biomolecules & Biomedicine |
| spelling | doaj-art-e65bcf1bf9f54400a645f70da5ade8892025-08-20T02:05:52ZengAssociation of Basic Medical Sciences of Federation of Bosnia and HerzegovinaBiomolecules & Biomedicine2831-08962831-090X2024-11-0110.17305/bb.2024.11218Therapeutic potential of Simvastatin in ALS: Enhanced axonal integrity and motor neuron survival through Apoa4 and Alb modulationSong Luo0Xiaorui Wang1Bo Ma2Dongliang Liu3Li Li4Lijin Wang5Ning Ding6Liangyu Zou7Jie Wang8Jialin Pan9Daoqian Sang10Huadong Zhou11Hongdang Qu12Yi Lu13Lijuan Yang14Department of Neurology, the First Affiliated Hospital of Bengbu Medical University, Bengbu, ChinaDepartment of Neurology, the First Affiliated Hospital of Bengbu Medical University, Bengbu, ChinaDepartment of Neurology, the First Affiliated Hospital of Bengbu Medical University, Bengbu, ChinaDepartment of Neurology, the First Affiliated Hospital of Bengbu Medical University, Bengbu, ChinaDepartment of Neurology, the First Affiliated Hospital of Bengbu Medical University, Bengbu, ChinaDepartment of Psychiatry, Bengbu Medical University, Bengbu, ChinaDepartment of Hematology, the First Affiliated Hospital of Bengbu Medical University, Bengbu, ChinaDepartment of Neurology, Shenzhen People’s Hospital, The Second Clinical Medical College, Jinan University, Shenzhen, ChinaInternational Medical Center (Department of Geriatric Medicine), Shenzhen University General Hospital, Shenzhen, ChinaDepartment of Internal Medicine, Second People’s Hospital, Longgang District, Shenzhen, ChinaDepartment of Neurology, the First Affiliated Hospital of Bengbu Medical University, Bengbu, ChinaDepartment of Neurology, the First Affiliated Hospital of Bengbu Medical University, Bengbu, ChinaDepartment of Neurology, the First Affiliated Hospital of Bengbu Medical University, Bengbu, ChinaDepartment of Neurology, the First Affiliated Hospital of Bengbu Medical University, Bengbu, ChinaDepartment of Pediatrics, the First Affiliated Hospital of Bengbu Medical University, Bengbu, ChinaAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the selective death of motor neurons in the spinal cord, brainstem, and motor cortex. This study investigates the effects of simvastatin on the G93A-copper/zinc superoxide dismutase (G93ASOD1) transgenic mouse model of ALS. The experiment included three groups: C57BL/6 wild-type (WT) mice, C57BL/6J SOD1G93A mice treated with PBS (SOD1G93A + PBS), and C57BL/6J SOD1G93A mice treated with simvastatin (SOD1G93A + simvastatin). The primary endpoints were survival rates, body weight changes, performance in pole climbing and suspension tests, and neurological deficit scores. Pathological changes were assessed using H&E staining, transmission electron microscopy, Nissl staining, and Masson staining. Proteomic and metabolomic analyses were performed to identify differentially expressed proteins (DEPs) and metabolites. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were used to measure gene expression. Although there were no significant differences in survival rates, body weight, pole climbing, and suspension test performance, or neurological deficit scores between the SOD1G93A + simvastatin and SOD1G93A + PBS groups, simvastatin treatment improved axonal organization within the spinal cord, increased the number of neurons, and reduced cytoplasmic swelling and gastrocnemius fibrosis. A total of 47 DEPs and 13 differential metabolites were identified between the SOD1G93A + PBS and SOD1G93A + simvastatin groups. Notably, the expression levels of Apoa4 and Alb were elevated in the SOD1G93A + simvastatin group compared to the SOD1G93A + PBS group. Our results suggest that simvastatin may have potential therapeutic effects in ALS, likely involving the modulation of Apoa4 and Alb expression. https://www.bjbms.org/ojs/index.php/bjbms/article/view/11218Simvastatinamyotrophic lateral sclerosistransgenic mouse modelApoa4Alb |
| spellingShingle | Song Luo Xiaorui Wang Bo Ma Dongliang Liu Li Li Lijin Wang Ning Ding Liangyu Zou Jie Wang Jialin Pan Daoqian Sang Huadong Zhou Hongdang Qu Yi Lu Lijuan Yang Therapeutic potential of Simvastatin in ALS: Enhanced axonal integrity and motor neuron survival through Apoa4 and Alb modulation Biomolecules & Biomedicine Simvastatin amyotrophic lateral sclerosis transgenic mouse model Apoa4 Alb |
| title | Therapeutic potential of Simvastatin in ALS: Enhanced axonal integrity and motor neuron survival through Apoa4 and Alb modulation |
| title_full | Therapeutic potential of Simvastatin in ALS: Enhanced axonal integrity and motor neuron survival through Apoa4 and Alb modulation |
| title_fullStr | Therapeutic potential of Simvastatin in ALS: Enhanced axonal integrity and motor neuron survival through Apoa4 and Alb modulation |
| title_full_unstemmed | Therapeutic potential of Simvastatin in ALS: Enhanced axonal integrity and motor neuron survival through Apoa4 and Alb modulation |
| title_short | Therapeutic potential of Simvastatin in ALS: Enhanced axonal integrity and motor neuron survival through Apoa4 and Alb modulation |
| title_sort | therapeutic potential of simvastatin in als enhanced axonal integrity and motor neuron survival through apoa4 and alb modulation |
| topic | Simvastatin amyotrophic lateral sclerosis transgenic mouse model Apoa4 Alb |
| url | https://www.bjbms.org/ojs/index.php/bjbms/article/view/11218 |
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