Analysis of the Biomarkers for Neurodegenerative Diseases in Aged Progranulin Deficient Mice
Neurodegenerative diseases are debilitating impairments that affect millions of people worldwide and are characterized by progressive degeneration of structure and function of the central or peripheral nervous system. Effective biomarkers for neurodegenerative diseases can be used to improve the dia...
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| Format: | Article |
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MDPI AG
2022-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/2/629 |
| _version_ | 1797493477700796416 |
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| author | Xiangli Zhao Sadaf Hasan Benjamin Liou Yi Lin Ying Sun Chuanju Liu |
| author_facet | Xiangli Zhao Sadaf Hasan Benjamin Liou Yi Lin Ying Sun Chuanju Liu |
| author_sort | Xiangli Zhao |
| collection | DOAJ |
| description | Neurodegenerative diseases are debilitating impairments that affect millions of people worldwide and are characterized by progressive degeneration of structure and function of the central or peripheral nervous system. Effective biomarkers for neurodegenerative diseases can be used to improve the diagnostic workup in the clinic as well as facilitate the development of effective disease-modifying therapies. Progranulin (PGRN) has been reported to be involved in various neurodegenerative disorders. Hence, in the current study we systematically compared the inflammation and accumulation of typical neurodegenerative disease markers in the brain tissue between PGRN knockout (PGRN KO) and wildtype (WT) mice. We found that PGRN deficiency led to significant neuron loss as well as activation of microglia and astrocytes in aged mice. Several characteristic neurodegenerative markers, including α-synuclein, TAR DNA-binding protein 43 (TDP-43), Tau, and β-amyloid, were all accumulated in the brain of PGRN-deficient mice as compared to WT mice. Moreover, higher aggregation of lipofuscin was observed in the brain tissue of PGRN-deficient mice compared with WT mice. In addition, the autophagy was also defective in the brain of PGRN-deficient mice, indicated by the abnormal expression level of autophagy marker LC3-II. Collectively, comprehensive assays support the idea that PGRN plays an important role during the development of neurodegenerative disease, indicating that PGRN might be a useful biomarker for neurodegenerative diseases in clinical settings. |
| first_indexed | 2024-03-10T01:20:33Z |
| format | Article |
| id | doaj.art-fe3755b30bf44b8d83470c4268999763 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T01:20:33Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-fe3755b30bf44b8d83470c42689997632023-11-23T14:01:34ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-01-0123262910.3390/ijms23020629Analysis of the Biomarkers for Neurodegenerative Diseases in Aged Progranulin Deficient MiceXiangli Zhao0Sadaf Hasan1Benjamin Liou2Yi Lin3Ying Sun4Chuanju Liu5Department of Orthopaedic Surgery, New York University Medical Center, New York, NY 10003, USADepartment of Orthopaedic Surgery, New York University Medical Center, New York, NY 10003, USAThe Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USAThe Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USAThe Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USADepartment of Orthopaedic Surgery, New York University Medical Center, New York, NY 10003, USANeurodegenerative diseases are debilitating impairments that affect millions of people worldwide and are characterized by progressive degeneration of structure and function of the central or peripheral nervous system. Effective biomarkers for neurodegenerative diseases can be used to improve the diagnostic workup in the clinic as well as facilitate the development of effective disease-modifying therapies. Progranulin (PGRN) has been reported to be involved in various neurodegenerative disorders. Hence, in the current study we systematically compared the inflammation and accumulation of typical neurodegenerative disease markers in the brain tissue between PGRN knockout (PGRN KO) and wildtype (WT) mice. We found that PGRN deficiency led to significant neuron loss as well as activation of microglia and astrocytes in aged mice. Several characteristic neurodegenerative markers, including α-synuclein, TAR DNA-binding protein 43 (TDP-43), Tau, and β-amyloid, were all accumulated in the brain of PGRN-deficient mice as compared to WT mice. Moreover, higher aggregation of lipofuscin was observed in the brain tissue of PGRN-deficient mice compared with WT mice. In addition, the autophagy was also defective in the brain of PGRN-deficient mice, indicated by the abnormal expression level of autophagy marker LC3-II. Collectively, comprehensive assays support the idea that PGRN plays an important role during the development of neurodegenerative disease, indicating that PGRN might be a useful biomarker for neurodegenerative diseases in clinical settings.https://www.mdpi.com/1422-0067/23/2/629Progranulinneurodegenerative diseasebraininflammationbiomarker |
| spellingShingle | Xiangli Zhao Sadaf Hasan Benjamin Liou Yi Lin Ying Sun Chuanju Liu Analysis of the Biomarkers for Neurodegenerative Diseases in Aged Progranulin Deficient Mice International Journal of Molecular Sciences Progranulin neurodegenerative disease brain inflammation biomarker |
| title | Analysis of the Biomarkers for Neurodegenerative Diseases in Aged Progranulin Deficient Mice |
| title_full | Analysis of the Biomarkers for Neurodegenerative Diseases in Aged Progranulin Deficient Mice |
| title_fullStr | Analysis of the Biomarkers for Neurodegenerative Diseases in Aged Progranulin Deficient Mice |
| title_full_unstemmed | Analysis of the Biomarkers for Neurodegenerative Diseases in Aged Progranulin Deficient Mice |
| title_short | Analysis of the Biomarkers for Neurodegenerative Diseases in Aged Progranulin Deficient Mice |
| title_sort | analysis of the biomarkers for neurodegenerative diseases in aged progranulin deficient mice |
| topic | Progranulin neurodegenerative disease brain inflammation biomarker |
| url | https://www.mdpi.com/1422-0067/23/2/629 |
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