ALS-Linked SOD1 Mutants Enhance Neurite Outgrowth and Branching in Adult Motor Neurons
Summary: Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disease characterized by motor neuron cell death. However, not all motor neurons are equally susceptible. Most of what we know about the surviving motor neurons comes from gene expression profiling; less is known...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-01-01
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| Series: | iScience |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004218302566 |
| _version_ | 1817977822668390400 |
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| author | Zachary Osking Jacob I. Ayers Ryan Hildebrandt Kristen Skruber Hilda Brown Daniel Ryu Amanda R. Eukovich Todd E. Golde David R. Borchelt Tracy-Ann Read Eric A. Vitriol |
| author_facet | Zachary Osking Jacob I. Ayers Ryan Hildebrandt Kristen Skruber Hilda Brown Daniel Ryu Amanda R. Eukovich Todd E. Golde David R. Borchelt Tracy-Ann Read Eric A. Vitriol |
| author_sort | Zachary Osking |
| collection | DOAJ |
| description | Summary: Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disease characterized by motor neuron cell death. However, not all motor neurons are equally susceptible. Most of what we know about the surviving motor neurons comes from gene expression profiling; less is known about their functional traits. We found that resistant motor neurons cultured from SOD1 ALS mouse models have enhanced axonal outgrowth and dendritic branching. They also have an increase in the number and size of actin-based structures like growth cones and filopodia. These phenotypes occur in cells cultured from presymptomatic mice and mutant SOD1 models that do not develop ALS but not in embryonic motor neurons. Enhanced outgrowth and upregulation of filopodia can be induced in wild-type adult cells by expressing mutant SOD1. These results demonstrate that mutant SOD1 can enhance the regenerative capability of ALS-resistant motor neurons. Capitalizing on this mechanism could lead to new therapeutic strategies. : Biological Sciences; Genetics; Neuroscience; Cell Biology Subject Areas: Biological Sciences, Genetics, Neuroscience, Cell Biology |
| first_indexed | 2024-04-13T22:21:32Z |
| format | Article |
| id | doaj.art-d70657e976174f1195ce5d2223963fe0 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-13T22:21:32Z |
| publishDate | 2019-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-d70657e976174f1195ce5d2223963fe02022-12-22T02:27:14ZengElsevieriScience2589-00422019-01-0111294304ALS-Linked SOD1 Mutants Enhance Neurite Outgrowth and Branching in Adult Motor NeuronsZachary Osking0Jacob I. Ayers1Ryan Hildebrandt2Kristen Skruber3Hilda Brown4Daniel Ryu5Amanda R. Eukovich6Todd E. Golde7David R. Borchelt8Tracy-Ann Read9Eric A. Vitriol10Department of Anatomy and Cell Biology, University of Florida, Gainesville, FL 32610, USADepartment of Neuroscience, University of Florida, Gainesville, FL 32610, USA; Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL 32610, USA; McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USADepartment of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610, USADepartment of Anatomy and Cell Biology, University of Florida, Gainesville, FL 32610, USADepartment of Neuroscience, University of Florida, Gainesville, FL 32610, USA; Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL 32610, USADepartment of Neuroscience, University of Florida, Gainesville, FL 32610, USA; Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL 32610, USADepartment of Anatomy and Cell Biology, University of Florida, Gainesville, FL 32610, USADepartment of Neuroscience, University of Florida, Gainesville, FL 32610, USA; Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL 32610, USA; McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USADepartment of Neuroscience, University of Florida, Gainesville, FL 32610, USA; Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL 32610, USA; McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USADepartment of Anatomy and Cell Biology, University of Florida, Gainesville, FL 32610, USA; Corresponding authorDepartment of Anatomy and Cell Biology, University of Florida, Gainesville, FL 32610, USA; Corresponding authorSummary: Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disease characterized by motor neuron cell death. However, not all motor neurons are equally susceptible. Most of what we know about the surviving motor neurons comes from gene expression profiling; less is known about their functional traits. We found that resistant motor neurons cultured from SOD1 ALS mouse models have enhanced axonal outgrowth and dendritic branching. They also have an increase in the number and size of actin-based structures like growth cones and filopodia. These phenotypes occur in cells cultured from presymptomatic mice and mutant SOD1 models that do not develop ALS but not in embryonic motor neurons. Enhanced outgrowth and upregulation of filopodia can be induced in wild-type adult cells by expressing mutant SOD1. These results demonstrate that mutant SOD1 can enhance the regenerative capability of ALS-resistant motor neurons. Capitalizing on this mechanism could lead to new therapeutic strategies. : Biological Sciences; Genetics; Neuroscience; Cell Biology Subject Areas: Biological Sciences, Genetics, Neuroscience, Cell Biologyhttp://www.sciencedirect.com/science/article/pii/S2589004218302566 |
| spellingShingle | Zachary Osking Jacob I. Ayers Ryan Hildebrandt Kristen Skruber Hilda Brown Daniel Ryu Amanda R. Eukovich Todd E. Golde David R. Borchelt Tracy-Ann Read Eric A. Vitriol ALS-Linked SOD1 Mutants Enhance Neurite Outgrowth and Branching in Adult Motor Neurons iScience |
| title | ALS-Linked SOD1 Mutants Enhance Neurite Outgrowth and Branching in Adult Motor Neurons |
| title_full | ALS-Linked SOD1 Mutants Enhance Neurite Outgrowth and Branching in Adult Motor Neurons |
| title_fullStr | ALS-Linked SOD1 Mutants Enhance Neurite Outgrowth and Branching in Adult Motor Neurons |
| title_full_unstemmed | ALS-Linked SOD1 Mutants Enhance Neurite Outgrowth and Branching in Adult Motor Neurons |
| title_short | ALS-Linked SOD1 Mutants Enhance Neurite Outgrowth and Branching in Adult Motor Neurons |
| title_sort | als linked sod1 mutants enhance neurite outgrowth and branching in adult motor neurons |
| url | http://www.sciencedirect.com/science/article/pii/S2589004218302566 |
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