| Intracellular targeting and clearance of oligomeric alpha-synuclein alleviates toxicity in mammalian cells. | |
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MedLine Citation:
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PMID: 19394405 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Intracellular clearance of toxic protein aggregates represents a promising therapeutic approach to treat protein-misfolding diseases such as Parkinson's and Huntington's diseases. Intracelluarly expressed antibody fragments or intrabodies can be used to bind specific intracellular targets. Addition of a non-traditional secretion signal sequence enables the intrabody to first bind its target inside the cell and then shuttle the bound target through the cell membrane, secreting it from the cell. We intracellularly expressed two different single chain antibody (scFv) fragments targeting either monomeric or oligomeric alpha-synuclein (a-syn), in a mammalian cell model that overexpresses a-syn. Two versions of each intrabody were studied, one with and one without the non-traditional secretion signal. The scFv targeting monomeric a-syn provided little or no reduction in toxicity induced by overexpression of a-syn, however binding and secretion of oligomeric a-syn totally reduced toxicity. Non-traditional intrabody secretion therefore represents an effective method to target and clear a variety of harmful intracellular species. |
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Authors:
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Bin Yuan; Michael R Sierks |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-04-24 |
Journal Detail:
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Title: Neuroscience letters Volume: 459 ISSN: 1872-7972 ISO Abbreviation: Neurosci. Lett. Publication Date: 2009 Jul |
Date Detail:
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Created Date: 2009-06-01 Completed Date: 2009-08-21 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7600130 Medline TA: Neurosci Lett Country: Ireland |
Other Details:
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Languages: eng Pagination: 16-8 Citation Subset: IM |
Affiliation:
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Department of Chemical Engineering, Arizona State University, Tempe, AZ 85287-6006, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Blotting, Western Cell Adhesion / physiology Cell Line Cell Survival / physiology Gene Transfer Techniques Green Fluorescent Proteins / genetics Humans Immunoglobulin Fragments / genetics, metabolism* alpha-Synuclein / metabolism*, secretion, toxicity* |
| Chemical | |
Reg. No./Substance:
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0/Immunoglobulin Fragments; 0/alpha-Synuclein; 147336-22-9/Green Fluorescent Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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