Cross-beta structure comprising amyloid-binding proteins and methods for detection of the cross-beta structure, for modulating cross-beta structures fibril formation and for modulating cross-beta structure-mediated toxicity

Abstract

The invention relates to the field of biochemistry, molecular biology, structural biology and medicine. More in particular, the invention relates to cross-β structures and the biological role of these cross-β structures. In one embodiment, the invention discloses a method for modulating extracellular protein degradation and/or protein clearance comprising modulating cross-β(beta) structure formation (and/or cross-β structure-mediated activity) of the protein present in the circulation.

1 - 35 . (canceled)  
     
     
         36 . A method for detecting a plaque involved in a conformational disease, the method comprising: 
 contacting a sample with an antibody capable of binding a cross-β structure epitope; and    detecting binding of the antibody to the cross-β structure epitope.    
     
     
         37 . A method for detecting a plaque involved in a conformational disease, the method comprising: 
 contacting a sample with a cross-β structure binding domain; and    detecting binding of the cross-β structure binding domain to the cross-β structure.    
     
     
         38 . The method according to  claim 36 , wherein said conformational disease is Alzheimers or diabetes.  
     
     
         39 - 47 . (canceled)  
     
     
         48 . A method for detecting cross-β structures in a sample, the method comprising: 
 contacting the sample with a compound capable of binding cross-β structures;    allowing the cross-β structures to bind to the compound; and    detecting a complex formed through binding of the compound to the cross-β structures.    
     
     
         49 . The method according to  claim 48 , wherein the sample is of a body fluid origin.  
     
     
         50 . The method according to  claim 49 , wherein the body fluid is selected from the group consisting of blood, serum, liquor, and combinations of any thereof.  
     
     
         51 . The method according to  claim 48 , wherein the compound capable of binding cross-β structures is: an antibody, a fragment, or a derivative thereof against cross-β structures; a tPA finger domain or a functional equivalent thereof; or a multiligand receptor for cross-β structures.  
     
     
         52 . The method according to  claim 48 , wherein the compound capable of binding cross-β structures is provided on a solid phase.  
     
     
         53 . A diagnostic device for carrying out the method according to  claim 48 , the diagnostic device comprising: 
 a sample container for holding a sample;    means for contacting the sample with a cross-β structure binding compound;    a cross-β structure binding compound; and    means for detecting bound cross-β structures.    
     
     
         54 . The diagnostic device of  claim 53 , further comprising means for separating unbound cross-β structures from bound cross-β structures.  
     
     
         55 . The diagnostic device of  claim 53 , wherein said cross-β compound is provided on a solid phase.  
     
     
         56 - 57 . (canceled)  
     
     
         58 . The method according to  claim 37 , wherein said conformational disease is Alzheimers or diabetes.  
     
     
         59 . The method according to  claim 36 , further comprising: 
 immobilizing the antibody capable of binding the cross-β structure epitope on a substrate.    
     
     
         60 . The method according to  claim 37 , wherein the cross-β structure binding domain is: an antibody, a fragment, or a derivative thereof against cross-β structures; a tPA finger domain or a functional equivalent thereof; or a multiligand receptor for cross-β structures.  
     
     
         61 . The method according to  claim 36 , wherein the sample is of a body fluid origin.  
     
     
         62 . The method according to  claim 61 , wherein the body fluid is selected from the group consisting of blood, serum, liquor, and combinations of any thereof.  
     
     
         63 . The method according to  claim 37 , wherein the sample is of a body fluid origin.  
     
     
         64 . The method according to  claim 63 , wherein the body fluid is selected from the group consisting of blood, serum, liquor, and combinations of any thereof.  
     
     
         65 . The method according to  claim 37 , further comprising: 
 immobilizing the cross-β structure binding domain on a substrate.