Document Detail


Intracellular targeting and clearance of oligomeric alpha-synuclein alleviates toxicity in mammalian cells.
MedLine Citation:
PMID:  19394405     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Bin Yuan; Michael R Sierks
Related Documents :
18216855 - Neurite arborization and mosaic spacing in the mouse retina require dscam.
1976215 - Processing and intracellular sorting of anglerfish and rat preprosomatostatins in mamma...
18245255 - Use of drosophila s2 cells as a model for studying ehrlichia chaffeensis infections.
19405035 - High-throughput generation of tagged stable cell lines for proteomic analysis.
11201085 - Intercellular action of nitric oxide increases cgmp in cerebellar purkinje cells.
18755185 - The alpha1 isoform of the na+/k+ atpase is up-regulated in dedifferentiated progenitor ...
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    
Affiliation:
Department of Chemical Engineering, Arizona State University, Tempe, AZ 85287-6006, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
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:
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


Previous Document:  The multi-faceted basis of vitamin B12 (cobalamin) neurotrophism in adult central nervous system: Le...
Next Document:  Inhibition of 6-hydroxydopamine-induced endoplasmic reticulum stress by l-carnosine in SH-SY5Y cells...