Small molecule drug discovery for Huntington's Disease.
Huntington's Disease (HD) is a rare neurodegenerative disease caused by mutation of the huntingtin gene that results in a protein with an expanded stretch of glutamine repeats (polyQ). Knowledge of validated targets is in its infancy, and thus, traditional target-based drug discovery strategies are of limited use. Alternative approaches are needed, and early attempts were aimed at identifying molecules that inhibited the aggregation of polyQ huntingtin fragments. More recently, phenotypic assays were used to find molecules able to reverse some of the pathogenic mechanisms of HD. Such discovery strategies have an impact on the configuration of screening cascades for effective translation of drug candidates toward clinical trials.
Fecke
Wolfgang
W
Siena Biotech S.p.A., Strada del Petriccio e Belriguardo 35, 53100 Siena, Italy.
Gianfriddo
Marco
M
Gaviraghi
Giovanni
G
Terstappen
Georg C
GC
Heitz
Freddy
F
D000818:Animals; D002449:Cell Aggregation / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000379:methods; D055808:Drug Discovery / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D040081:Protein Array Analysis; D054852:Small Molecule Libraries; D014158:Transcription, Genetic / Q000187:drug effects
C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D054852:Small Molecule Libraries