Neurodegenerative Protein Aggregation Inhibition Methods and Compounds

Abstract

Methods and compositions are provided for reducing aggregation of neurodegenerative proteins associated with neurotoxicity or other proteins. The compounds comprise a first domain or targeting element for binding to the target proteins linked to a second domain or recruiting element that binds to an aggregation inhibiting protein, e.g. a prolyl isomerase. By associating the aggregating forming proteins or neuronal cells under conditions where aggregating proteins are produced with the compound and the aggregation inhibiting protein, aggregation is reduced. The subject agents can be used in assays, investigating the etiology of the neuronal diseases and for prophylaxis and therapy.

1 . A method for diminishing the presence of protein aggregates in an environment susceptible to the formation of a protein aggregate, said method comprising:
 introducing into said environment a compound having two domains, a first domain that binds to a protein aggregation having at least two monomers, and a second domain binding to an aggregation diminishing protein,   whereby the presence of aggregations is diminished.   
     
     
         2 . A method according to  claim 1 , wherein said aggregation diminishing protein sterically interferes with the formation of aggregations. 
     
     
         3 . A method according to  claim 1 , wherein said aggregation diminishing protein enzymatically modifies said monomers to inhibit aggregation. 
     
     
         4 . A method for reducing aggregation of neurodegenerative proteins, said method comprising:
 associating neurodegenerative proteins with a compound comprising a first domain binding to said neurodegenerative proteins linked to a second domain binding to an aggregation formation reducing protein.   whereby aggregations are diminished.   
     
     
         5 . A method according to  claim 4 , wherein said aggregation formation reducing protein is a prolyl isomerase. 
     
     
         6 - 7 . (canceled) 
     
     
         8 . A method according to  claim 4 , wherein said first domain is a polycyclic compound. 
     
     
         9 . A method according to  claim 5 , wherein said polycyclic compound comprises a biphenyl or stilbene. 
     
     
         10 . A compound comprising a polycyclic domain binding to neurodegenerative proteins linked to a prolyl isomerase-binding domain. 
     
     
         11 - 17 . (canceled)