Optineurin overexpression ameliorates neurodegeneration through regulating neuroinflammation and mitochondrial quality in a murine model of amyotrophic lateral sclerosis
IntroductionAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the loss of motor neurons (MNs). Genetic mutations in Optineurin (OPTN) and Superoxide Dismutase 1 (SOD1) have been identified as causal factors for ALS. OPTN immunopositive inclusions have been confirmed...
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Aging Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2025.1522073/full |
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| author | Shumin Zhao Shumin Zhao Ranran Chen Ranran Chen Yi An Yali Zhang Yali Zhang Cheng Ma Ying Gao Ying Gao Yanchao Lu Yanchao Lu Fei Yang Fei Yang Xue Bai Xue Bai Jingjing Zhang Jingjing Zhang Jingjing Zhang |
| author_facet | Shumin Zhao Shumin Zhao Ranran Chen Ranran Chen Yi An Yali Zhang Yali Zhang Cheng Ma Ying Gao Ying Gao Yanchao Lu Yanchao Lu Fei Yang Fei Yang Xue Bai Xue Bai Jingjing Zhang Jingjing Zhang Jingjing Zhang |
| author_sort | Shumin Zhao |
| collection | DOAJ |
| description | IntroductionAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the loss of motor neurons (MNs). Genetic mutations in Optineurin (OPTN) and Superoxide Dismutase 1 (SOD1) have been identified as causal factors for ALS. OPTN immunopositive inclusions have been confirmed in the cases of ALS with SOD1 mutations. However, the role of the OPTN gene in ALS caused by SOD1 mutations is ambiguous.MethodsThe murine Optn lentivirus and empty vector lentivirus were injected into SOD1G93A mice after discovering variations in Optn expression over time. The phenotype onset date, life span, locomotor activity, and pathological changes in the spinal cord were determined and recorded subsequently. In addition, the influences on cellular apoptosis, mitochondrial dynamics, mitophagy, and neuroinflammation were further investigated.ResultsOptn expression was increased in the spinal cord of SOD1G93A mice at the pre-symptomatic phase, but decreased after disease onset. Optn overexpression led to a 9.7% delay in the onset of disease and improved motor performance in SOD1G93A mice. Optn overexpression also ameliorated the MNs loss by 46.8%. Moreover, all these ameliorating effects induced by Optn overexpression might be due to the inhibition of cellular apoptosis, improvement of mitochondrial quality, regulation of mitochondrial dynamics, promotion of mitophagy, and anti-inflammatory properties.ConclusionOur data demonstrate that Optn overexpression protects MNs, inhibites cellular apoptosis, improves mitochondrial quality and regulates neuroinflamation in SOD1G93A mice at the pre-symptomatic stage. |
| format | Article |
| id | doaj-art-6423f0fd07ca4aaba589c449a3b421d0 |
| institution | Kabale University |
| issn | 1663-4365 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj-art-6423f0fd07ca4aaba589c449a3b421d02025-02-07T06:49:43ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652025-02-011710.3389/fnagi.2025.15220731522073Optineurin overexpression ameliorates neurodegeneration through regulating neuroinflammation and mitochondrial quality in a murine model of amyotrophic lateral sclerosisShumin Zhao0Shumin Zhao1Ranran Chen2Ranran Chen3Yi An4Yali Zhang5Yali Zhang6Cheng Ma7Ying Gao8Ying Gao9Yanchao Lu10Yanchao Lu11Fei Yang12Fei Yang13Xue Bai14Xue Bai15Jingjing Zhang16Jingjing Zhang17Jingjing Zhang18Department of Neurology, Chifeng Municipal Hospital, Chifeng, ChinaChifeng Clinical Medical College of Inner Mongolia Medical University, Chifeng, ChinaDepartment of Neurology, Chifeng Municipal Hospital, Chifeng, ChinaChifeng Clinical Medical College of Inner Mongolia Medical University, Chifeng, ChinaDepartment of Neurology, Chifeng Municipal Hospital, Chifeng, ChinaDepartment of Neurology, Chifeng Municipal Hospital, Chifeng, ChinaChifeng Clinical Medical College of Inner Mongolia Medical University, Chifeng, ChinaMedical Research Center, Chifeng Municipal Hospital, Chifeng, ChinaDepartment of Neurology, Chifeng Municipal Hospital, Chifeng, ChinaChifeng Clinical Medical College of Inner Mongolia Medical University, Chifeng, ChinaDepartment of Neurology, Chifeng Municipal Hospital, Chifeng, ChinaChifeng Clinical Medical College of Inner Mongolia Medical University, Chifeng, ChinaChifeng Clinical Medical College of Inner Mongolia Medical University, Chifeng, ChinaIntensive Care Unit, Chifeng Municipal Hospital, Chifeng, ChinaDepartment of Neurology, Chifeng Municipal Hospital, Chifeng, ChinaChifeng Clinical Medical College of Inner Mongolia Medical University, Chifeng, ChinaDepartment of Neurology, Chifeng Municipal Hospital, Chifeng, ChinaChifeng Clinical Medical College of Inner Mongolia Medical University, Chifeng, ChinaMedical Research Center, Chifeng Municipal Hospital, Chifeng, ChinaIntroductionAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the loss of motor neurons (MNs). Genetic mutations in Optineurin (OPTN) and Superoxide Dismutase 1 (SOD1) have been identified as causal factors for ALS. OPTN immunopositive inclusions have been confirmed in the cases of ALS with SOD1 mutations. However, the role of the OPTN gene in ALS caused by SOD1 mutations is ambiguous.MethodsThe murine Optn lentivirus and empty vector lentivirus were injected into SOD1G93A mice after discovering variations in Optn expression over time. The phenotype onset date, life span, locomotor activity, and pathological changes in the spinal cord were determined and recorded subsequently. In addition, the influences on cellular apoptosis, mitochondrial dynamics, mitophagy, and neuroinflammation were further investigated.ResultsOptn expression was increased in the spinal cord of SOD1G93A mice at the pre-symptomatic phase, but decreased after disease onset. Optn overexpression led to a 9.7% delay in the onset of disease and improved motor performance in SOD1G93A mice. Optn overexpression also ameliorated the MNs loss by 46.8%. Moreover, all these ameliorating effects induced by Optn overexpression might be due to the inhibition of cellular apoptosis, improvement of mitochondrial quality, regulation of mitochondrial dynamics, promotion of mitophagy, and anti-inflammatory properties.ConclusionOur data demonstrate that Optn overexpression protects MNs, inhibites cellular apoptosis, improves mitochondrial quality and regulates neuroinflamation in SOD1G93A mice at the pre-symptomatic stage.https://www.frontiersin.org/articles/10.3389/fnagi.2025.1522073/fullamyotrophic lateral sclerosisapoptosismitochondrial qualityneuroinflammationoptineurin |
| spellingShingle | Shumin Zhao Shumin Zhao Ranran Chen Ranran Chen Yi An Yali Zhang Yali Zhang Cheng Ma Ying Gao Ying Gao Yanchao Lu Yanchao Lu Fei Yang Fei Yang Xue Bai Xue Bai Jingjing Zhang Jingjing Zhang Jingjing Zhang Optineurin overexpression ameliorates neurodegeneration through regulating neuroinflammation and mitochondrial quality in a murine model of amyotrophic lateral sclerosis Frontiers in Aging Neuroscience amyotrophic lateral sclerosis apoptosis mitochondrial quality neuroinflammation optineurin |
| title | Optineurin overexpression ameliorates neurodegeneration through regulating neuroinflammation and mitochondrial quality in a murine model of amyotrophic lateral sclerosis |
| title_full | Optineurin overexpression ameliorates neurodegeneration through regulating neuroinflammation and mitochondrial quality in a murine model of amyotrophic lateral sclerosis |
| title_fullStr | Optineurin overexpression ameliorates neurodegeneration through regulating neuroinflammation and mitochondrial quality in a murine model of amyotrophic lateral sclerosis |
| title_full_unstemmed | Optineurin overexpression ameliorates neurodegeneration through regulating neuroinflammation and mitochondrial quality in a murine model of amyotrophic lateral sclerosis |
| title_short | Optineurin overexpression ameliorates neurodegeneration through regulating neuroinflammation and mitochondrial quality in a murine model of amyotrophic lateral sclerosis |
| title_sort | optineurin overexpression ameliorates neurodegeneration through regulating neuroinflammation and mitochondrial quality in a murine model of amyotrophic lateral sclerosis |
| topic | amyotrophic lateral sclerosis apoptosis mitochondrial quality neuroinflammation optineurin |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2025.1522073/full |
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