Document Detail

Intracellular targeting and clearance of oligomeric alpha-synuclein alleviates toxicity in mammalian cells.
MedLine Citation:
PMID:  19394405     Owner:  NLM     Status:  MEDLINE    
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.
Bin Yuan; Michael R Sierks
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-04-24
Journal Detail:
Title:  Neuroscience letters     Volume:  459     ISSN:  1872-7972     ISO Abbreviation:  Neurosci. Lett.     Publication Date:  2009 Jul 
Date Detail:
Created Date:  2009-06-01     Completed Date:  2009-08-21     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7600130     Medline TA:  Neurosci Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  16-8     Citation Subset:  IM    
Department of Chemical Engineering, Arizona State University, Tempe, AZ 85287-6006, USA.
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MeSH Terms
Blotting, Western
Cell Adhesion / physiology
Cell Line
Cell Survival / physiology
Gene Transfer Techniques
Green Fluorescent Proteins / genetics
Immunoglobulin Fragments / genetics,  metabolism*
alpha-Synuclein / metabolism*,  secretion,  toxicity*
Reg. No./Substance:
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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