Single chain variable fragment antibodies block aggregation and toxicity induced by familial ALS-linked mutant forms of SOD1
| Autor: | Brian K. Kay, Sujatha P. Koduvayur, John D. Pavlovic, Raymond P. Roos, Ghanashyam D. Ghadge |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
medicine.drug_class
Blotting Western Mutant SOD1 Enzyme-Linked Immunosorbent Assay Single chain fragments of variable region antibodies Monoclonal antibody Article lcsh:RC321-571 Superoxide Dismutase-1 Mutant superoxide dismutase type 1 medicine Humans Single-chain variable fragment Biotinylation Cloning Molecular Amyotrophic lateral sclerosis Immunoglobulin Fragments lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Genetics Cell Death biology Superoxide Dismutase Motor neuron medicine.disease Molecular biology medicine.anatomical_structure Neurology Toxicity biology.protein Familial amyotrophic lateral sclerosis scFvs ALS Antibody Bacteriophage M13 |
| Zdroj: | Neurobiology of Disease, Vol 56, Iss, Pp 74-78 (2013) |
| ISSN: | 0969-9961 |
| DOI: | 10.1016/j.nbd.2013.04.007 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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