Compositions and Methods for Suppressing MSUT2

Abstract

Described herein are compositions and methods for treating Alzheimer's disease or dementia. The compositions include mammalian suppressor of taupathy 2 inhibitors (MSUT2). The MSUT2 inhibitors can be small interfering RNAs, guide RNAs, or small molecules. The methods include reducing accumulation of phosphorylated and aggregated human tau.

1 .- 89 . (canceled) 
     
     
         90 . A method of screening for compounds capable of inhibiting MSUT2 binding to poly(A) RNA, the method comprising:
 (a) introducing at least one candidate compound into a mixture, wherein the mixture comprises poly(A) RNA, PABPN1, and MSUT2;   (b) incubating the mixture under conditions in which PABPN1 is capable of stimulating RNA polyadenylation in the absence of the candidate compound;   (c) determining whether the candidate compound inhibits MSUT2 binding to the poly(A) RNA by measuring RNA polyadenylation of the poly(A) RNA, wherein absence of RNA polyadenylation indicates that the candidate compound inhibits MSUT2 binding to poly(A) RNA; and   (d) selecting the candidate compound which inhibits MSUT2 binding to poly(A) RNA.   
     
     
         91 . The method of  claim 90 , further comprising purifying the selected candidate compound. 
     
     
         92 . The method of  claim 90 , further comprising isolating the selected candidate compound. 
     
     
         93 . A method for screening compounds for pharmacological intervention in tauopathy disorders, the method comprising:
 (a) introducing at least one candidate compound into a mixture, wherein the mixture comprises poly(A) RNA, PABPN1, and MSUT2;   (b) incubating the mixture under conditions in which PABPN1 is capable of stimulating RNA polyadenylation in the absence of the candidate compound;   (c) determining whether the candidate compound inhibits MSUT2 binding to the poly(A) RNA by measuring RNA polyadenylation of the poly(A) RNA, wherein absence of RNA polyadenylation indicates that the candidate compound inhibits MSUT2 binding to poly(A) RNA; and   (d) selecting the candidate compound which inhibits MSUT2 binding to poly(A) RNA.   
     
     
         94 . The method of  claim 93 , further comprising purifying the selected candidate compound. 
     
     
         95 . The method of  claim 93 , further comprising isolating the selected candidate compound.