Presenilin-1 Protects against Neuronal Apoptosis Caused by Its Interacting Protein PAG
Mutations in the presenilin-1 (PS-1) gene account for a significant fraction of familial Alzheimer's disease. The biological function of PS-1 is not well understood. We report here that the proliferation-associated gene (PAG) product, a protein of the thioredoxin peroxidase family, interacts wi...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2002-03-01
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| Series: | Neurobiology of Disease |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996101904723 |
| _version_ | 1818673395370295296 |
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| author | Yan Zhou Wanjiang Zhang Rachael Easton James W. Ray Patricia Lampe Zhihong Jiang Anne L. Brunkan Alison Goate Eugene M. Johnson Jane Y. Wu |
| author_facet | Yan Zhou Wanjiang Zhang Rachael Easton James W. Ray Patricia Lampe Zhihong Jiang Anne L. Brunkan Alison Goate Eugene M. Johnson Jane Y. Wu |
| author_sort | Yan Zhou |
| collection | DOAJ |
| description | Mutations in the presenilin-1 (PS-1) gene account for a significant fraction of familial Alzheimer's disease. The biological function of PS-1 is not well understood. We report here that the proliferation-associated gene (PAG) product, a protein of the thioredoxin peroxidase family, interacts with PS-1. Microinjection of a plasmid expressing PAG into superior cervical ganglion (SCG) sympathetic neurons in primary cultures led to apoptosis. Microinjection of plasmids expressing wild-type PS-1 or a PS-1 mutant with a deletion of exon 10 (PS1dE10) by themselves had no effect on the survival of primary SCG neurons. However, co-injection of wild-type PS-1 with PAG prevented neuronal death, whereas co-injection with the mutant PS-1 did not affect PAG-induced apoptosis. Furthermore, overexpression of PAG accelerated SCG neuronal death induced by nerve growth factor deprivation. This sensitizing effect was also blocked by wild-type PS-1, but not by PS1dE10. These results establish an assay for studying the function of PS-1 in primary neurons, reveal the neurotoxicity of a thioredoxin peroxidase, demonstrate a neuroprotective activity of the wild-type PS-1, and suggest possible involvement of defective neuroprotection by PS-1 mutants in neurodegeneration. |
| first_indexed | 2024-12-17T07:55:07Z |
| format | Article |
| id | doaj.art-ef6fa62f406e4ba9bd34e97cfda4e6b2 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-17T07:55:07Z |
| publishDate | 2002-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-ef6fa62f406e4ba9bd34e97cfda4e6b22022-12-21T21:57:45ZengElsevierNeurobiology of Disease1095-953X2002-03-0192126138Presenilin-1 Protects against Neuronal Apoptosis Caused by Its Interacting Protein PAGYan Zhou0Wanjiang Zhang1Rachael Easton2James W. Ray3Patricia Lampe4Zhihong Jiang5Anne L. Brunkan6Alison Goate7Eugene M. Johnson8Jane Y. Wu9Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, 63110; Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri, 63110; Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, 63110; Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, 63110Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, 63110; Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri, 63110; Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, 63110; Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, 63110Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, 63110; Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri, 63110; Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, 63110; Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, 63110Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, 63110; Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri, 63110; Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, 63110; Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, 63110Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, 63110; Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri, 63110; Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, 63110; Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, 63110Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, 63110; Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri, 63110; Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, 63110; Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, 63110Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, 63110; Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri, 63110; Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, 63110; Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, 63110Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, 63110; Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri, 63110; Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, 63110; Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, 63110Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, 63110; Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri, 63110; Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, 63110; Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, 63110Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, 63110; Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri, 63110; Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, 63110; Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, 63110Mutations in the presenilin-1 (PS-1) gene account for a significant fraction of familial Alzheimer's disease. The biological function of PS-1 is not well understood. We report here that the proliferation-associated gene (PAG) product, a protein of the thioredoxin peroxidase family, interacts with PS-1. Microinjection of a plasmid expressing PAG into superior cervical ganglion (SCG) sympathetic neurons in primary cultures led to apoptosis. Microinjection of plasmids expressing wild-type PS-1 or a PS-1 mutant with a deletion of exon 10 (PS1dE10) by themselves had no effect on the survival of primary SCG neurons. However, co-injection of wild-type PS-1 with PAG prevented neuronal death, whereas co-injection with the mutant PS-1 did not affect PAG-induced apoptosis. Furthermore, overexpression of PAG accelerated SCG neuronal death induced by nerve growth factor deprivation. This sensitizing effect was also blocked by wild-type PS-1, but not by PS1dE10. These results establish an assay for studying the function of PS-1 in primary neurons, reveal the neurotoxicity of a thioredoxin peroxidase, demonstrate a neuroprotective activity of the wild-type PS-1, and suggest possible involvement of defective neuroprotection by PS-1 mutants in neurodegeneration.http://www.sciencedirect.com/science/article/pii/S0969996101904723 |
| spellingShingle | Yan Zhou Wanjiang Zhang Rachael Easton James W. Ray Patricia Lampe Zhihong Jiang Anne L. Brunkan Alison Goate Eugene M. Johnson Jane Y. Wu Presenilin-1 Protects against Neuronal Apoptosis Caused by Its Interacting Protein PAG Neurobiology of Disease |
| title | Presenilin-1 Protects against Neuronal Apoptosis Caused by Its Interacting Protein PAG |
| title_full | Presenilin-1 Protects against Neuronal Apoptosis Caused by Its Interacting Protein PAG |
| title_fullStr | Presenilin-1 Protects against Neuronal Apoptosis Caused by Its Interacting Protein PAG |
| title_full_unstemmed | Presenilin-1 Protects against Neuronal Apoptosis Caused by Its Interacting Protein PAG |
| title_short | Presenilin-1 Protects against Neuronal Apoptosis Caused by Its Interacting Protein PAG |
| title_sort | presenilin 1 protects against neuronal apoptosis caused by its interacting protein pag |
| url | http://www.sciencedirect.com/science/article/pii/S0969996101904723 |
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