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filingDate 2010-08-27-04:00^^<http://www.w3.org/2001/XMLSchema#date>
publicationDate 2013-01-31-04:00^^<http://www.w3.org/2001/XMLSchema#date>
publicationNumber JP-2013503112-A
titleOfInvention Use of holotoxin to reduce endoplasmic reticulum-related degradation of misfolded proteins
abstract Use of holotoxins to reduce endoplasmic reticulum associated degradation (ERAD) of misfolded or abnormally folded proteins is provided. Thus, holotoxins can be used in methods of treating diseases associated with ERAD. Examples of misfolded proteins that are degraded by ER include cystic fibrosis transmembrane conductance regulator (CFTR) ΔF508 mutant protein, multidrug resistance 1 (MDR1) misfolded mutant (G268V), and Gaucher disease cells Glucocerebrosidase (GCC) enzyme. Examples of suitable holotoxins include ricin, Shiga toxin, exotoxin A, toxin encoded on a plasmid, cholera toxin, and verotoxin 1 (VT1). VT1 is also known as Vero toxin A, Shiga-like toxin 1, Shiga-like toxin 1, or Shiga toxin type 1. Non-toxic inactive VT1 in which important residues in the A subunit active site have been mutated, for example, the Y77S mutation and the E167Q mutation, can also be used.
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