Single chain variable fragment antibodies block aggregation and toxicity induced by familial ALS-linked mutant forms of SOD1
Approximately 10% of amyotrophic lateral sclerosis (ALS) cases are familial (known as FALS) with an autosomal dominant inheritance pattern, and ~25% of FALS cases are caused by mutations in Cu/Zn superoxide dismutase (SOD1). There is convincing evidence that mutant SOD1 (mtSOD1) kills motor neurons...
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| Format: | Article |
| Language: | English |
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Elsevier
2013-08-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996113001216 |
| _version_ | 1818574392544722944 |
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| author | Ghanashyam D. Ghadge John D. Pavlovic Sujatha P. Koduvayur Brian K. Kay Raymond P. Roos |
| author_facet | Ghanashyam D. Ghadge John D. Pavlovic Sujatha P. Koduvayur Brian K. Kay Raymond P. Roos |
| author_sort | Ghanashyam D. Ghadge |
| collection | DOAJ |
| description | Approximately 10% of amyotrophic lateral sclerosis (ALS) cases are familial (known as FALS) with an autosomal dominant inheritance pattern, and ~25% of FALS cases are caused by mutations in Cu/Zn superoxide dismutase (SOD1). There is convincing evidence that mutant SOD1 (mtSOD1) kills motor neurons (MNs) because of a gain-of-function toxicity, most likely related to aggregation of mtSOD1. A number of recent reports have suggested that antibodies can be used to treat mtSOD1-induced FALS. To follow up on the use of antibodies as potential therapeutics, we generated single chain fragments of variable region antibodies (scFvs) against SOD1, and then expressed them as ‘intrabodies’ within a motor neuron cell line. In the present study, we describe isolation of human scFvs that interfere with mtSOD1 in vitro aggregation and toxicity. These scFvs may have therapeutic potential in sporadic ALS, as well as FALS, given that sporadic ALS may also involve abnormalities in the SOD1 protein or activity. |
| first_indexed | 2024-12-15T00:26:03Z |
| format | Article |
| id | doaj.art-baa71045168d47a78b070779a5f94cc1 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-15T00:26:03Z |
| publishDate | 2013-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-baa71045168d47a78b070779a5f94cc12022-12-21T22:42:10ZengElsevierNeurobiology of Disease1095-953X2013-08-01567478Single chain variable fragment antibodies block aggregation and toxicity induced by familial ALS-linked mutant forms of SOD1Ghanashyam D. Ghadge0John D. Pavlovic1Sujatha P. Koduvayur2Brian K. Kay3Raymond P. Roos4Department of Neurology, University of Chicago Medical Center, 5841 S. Maryland Avenue, MC2030, Chicago, IL 60637, USADepartment of Biological Sciences, University of Illinois at Chicago, 900 S. Ashland Ave., Molecular Biology Research Building, Room 4318, (M/C 567), Chicago, IL 60607, USADepartment of Biological Sciences, University of Illinois at Chicago, 900 S. Ashland Ave., Molecular Biology Research Building, Room 4318, (M/C 567), Chicago, IL 60607, USADepartment of Biological Sciences, University of Illinois at Chicago, 900 S. Ashland Ave., Molecular Biology Research Building, Room 4318, (M/C 567), Chicago, IL 60607, USADepartment of Neurology, University of Chicago Medical Center, 5841 S. Maryland Avenue, MC2030, Chicago, IL 60637, USA; Corresponding author at: Department of Neurology/MC2030, University of Chicago Medical Center, 5841 S. Maryland Ave., Chicago, IL 60637, USA. Fax: +1 773 834 9089.Approximately 10% of amyotrophic lateral sclerosis (ALS) cases are familial (known as FALS) with an autosomal dominant inheritance pattern, and ~25% of FALS cases are caused by mutations in Cu/Zn superoxide dismutase (SOD1). There is convincing evidence that mutant SOD1 (mtSOD1) kills motor neurons (MNs) because of a gain-of-function toxicity, most likely related to aggregation of mtSOD1. A number of recent reports have suggested that antibodies can be used to treat mtSOD1-induced FALS. To follow up on the use of antibodies as potential therapeutics, we generated single chain fragments of variable region antibodies (scFvs) against SOD1, and then expressed them as ‘intrabodies’ within a motor neuron cell line. In the present study, we describe isolation of human scFvs that interfere with mtSOD1 in vitro aggregation and toxicity. These scFvs may have therapeutic potential in sporadic ALS, as well as FALS, given that sporadic ALS may also involve abnormalities in the SOD1 protein or activity.http://www.sciencedirect.com/science/article/pii/S0969996113001216Familial amyotrophic lateral sclerosisMutant superoxide dismutase type 1Amyotrophic lateral sclerosisALSSingle chain fragments of variable region antibodiesscFvs |
| spellingShingle | Ghanashyam D. Ghadge John D. Pavlovic Sujatha P. Koduvayur Brian K. Kay Raymond P. Roos Single chain variable fragment antibodies block aggregation and toxicity induced by familial ALS-linked mutant forms of SOD1 Neurobiology of Disease Familial amyotrophic lateral sclerosis Mutant superoxide dismutase type 1 Amyotrophic lateral sclerosis ALS Single chain fragments of variable region antibodies scFvs |
| title | Single chain variable fragment antibodies block aggregation and toxicity induced by familial ALS-linked mutant forms of SOD1 |
| title_full | Single chain variable fragment antibodies block aggregation and toxicity induced by familial ALS-linked mutant forms of SOD1 |
| title_fullStr | Single chain variable fragment antibodies block aggregation and toxicity induced by familial ALS-linked mutant forms of SOD1 |
| title_full_unstemmed | Single chain variable fragment antibodies block aggregation and toxicity induced by familial ALS-linked mutant forms of SOD1 |
| title_short | Single chain variable fragment antibodies block aggregation and toxicity induced by familial ALS-linked mutant forms of SOD1 |
| title_sort | single chain variable fragment antibodies block aggregation and toxicity induced by familial als linked mutant forms of sod1 |
| topic | Familial amyotrophic lateral sclerosis Mutant superoxide dismutase type 1 Amyotrophic lateral sclerosis ALS Single chain fragments of variable region antibodies scFvs |
| url | http://www.sciencedirect.com/science/article/pii/S0969996113001216 |
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