CROSS-ß STRUCTURE COMPRISING AMYLOID-BINDING PROTEINS AND METHODS FOR DETECTION OF THE CROSS-ß STRUCTURE, FOR MODULATING CROSS-ß STRUCTURES FIBER FORMATION AND FOR MODULATING CROSS-ß 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 .- 26 . (canceled) 
     
     
         27 . A method for removing cross-β structures, the method comprising:
 administering a compound able to bind to a cross-β structure to a subject in need thereof. 
 
     
     
         28 . A method for diminishing plaques involved in a conformation disease in a subject, the method comprising:
 administering a compound able to bind to a cross-β structure to a subject suffering from a conformation disease.   
     
     
         29 . The method according to  claim 28 , wherein the compound is a peptide able to bind to the cross-β structure. 
     
     
         30 . The method according to  claim 28 , wherein the compound comprises tPA, a compound having tPA-like activity, or a functional equivalent or a functional fragment of tPA or a compound having tPA-like activity able to bind to the cross-β structure. 
     
     
         31 . The method according to  claim 30 , wherein the functional fragment comprises a finger domain. 
     
     
         32 . The method according to  claim 29 , wherein the peptide is an antibody, or an antibody fragment able to bind to cross-β structure. 
     
     
         33 .- 35 . (canceled) 
     
     
         36 . A method for detecting a plaque involved in a conformational disease, the method comprising:
 contacting a sample with an antibody able to bind 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 the disease is Alzheimer's disease or diabetes. 
     
     
         39 .- 57 . (canceled) 
     
     
         58 . A method for diminishing plaques involved in a disease in a subject, the method comprising:
 administering, to a subject in need thereof, a compound able to directly bind to a cross-β structure in a protein in the subject, for the purpose of allowing the subject to remove the cross-β structure,   
       so as to diminish plaques in the subject, 
       wherein the compound is selected form the group consisting of
 an antibody specific for a crossbeta structure, 
 a compound that comprises a fibronectin type I (“finger”) domain or finger domain selected form the group consisting of a finger domain of Factor XII, a finger domain of Hepatocyte Growth Factor activator, and a finger domain of fibronectin, 
 a compound that consists of one or more finger domains, and 
 recombinant tPA. 
 
     
     
         59 . A method for removing cross-β structure in protein of a subject, the method comprising:
 administering a compound able to directly bind to a cross-β structure to a subject in need thereof, so as to allow the subject's metabolism to remove cross-β structure in the subject, wherein the compound is selected from the group consisting of 
 an antibody specific for a crossbeta structure, 
 a compound that comprises a fibronectin type I (“finger”) domain of finger domain selected from the group consisting of a finger domain of Factor XII, a finger domain of Hepatocyte Growth Factor activator, and a finger domain of fibronectin, 
 a compound that consists of one or more finger domains, and 
 recombinant tPA. 
 
     
     
         60 . The method according to  claim 58 , wherein the disease is selected from the group consisting of Alzheimer's disease, an amyloidosis-type disease, atherosclerosis, diabetes, thrombosis, Multiple Sclerosis, autoimmune disease(s), neuronal disease(s), epilepsy, bleeding, cancer, sepsis, rheumatoid arthritis, Parkinson's disease, and a combination of any thereof. 
     
     
         61 . The method according to  claim 59 , wherein the disease is selected from the group consisting of Alzheimer's disease, an amyloidosis-type disease, atherosclerosis, diabetes, thrombosis, Multiple Sclerosis, autoimmune disease(s), neuronal disease, epilepsy, bleeding, cancer, sepsis, rheumatoid arthritis, Parkinson's disease, and combinations of any thereof. 
     
     
         62 . A method for diminishing plaques involved in a disease in a subject in need thereof, the method comprising:
 administering to the subject a compound able to directly bind to a cross-β structure in a protein in the subject, for the purpose of allowing the subject to remove the cross-β structure,   so as to diminish plaques in the subject,   wherein the compound comprises a receptor for a protein that comprises cross-β structure, and   wherein the disease is selected from the group consisting of an amyloidosis-type disease, atherosclerosis, diabetes, thrombosis, Multiple Sclerosis, autoimmune disease(s), neuronal disease, epilepsy, bleeding, cancer, sepsis, rheumatoid arthritis, Parkinson's disease, and a combination of any thereof.   
     
     
         63 . A method for removing cross-β structures in proteins of a subject in need thereof, the method comprising:
 administering a compound able to directly bind to a cross-β structure to the subject, so as to allow the subject's metabolism to remove cross-β structures in the subject, 
 wherein the compound comprises a receptor for a protein that comprises cross-β structure, and wherein the disease is selected from the group consisting of an amyloidosis-type disease, atherosclerosis, diabetes, thrombosis, Multiple Sclerosis, autoimmune disease(s), neuronal disease(s), epilepsy, bleeding, cancer, sepsis, rheumatoid arthritis, Parkinson's disease, and a combination of any thereof. 
 
     
     
         64 . The method according to  claim 37 , wherein the disease is Alzheimer's disease or diabetes.