title: Evaluation of histone deacetylase inhibitors as therapeutics for neurodegenerative diseases.
abstract: Various neurodegenerative diseases are associated with aberrant gene expression. We recently identified a novel class of pimelic o-aminobenzamide histone deacetylase (HDAC) inhibitors that show promise as therapeutics in the neurodegenerative diseases Friedreich's ataxia (FRDA) and Huntington's disease (HD). Here, we describe the various techniques used in our laboratories to dissect mechanisms of gene silencing in FRDA and HD, and to test our HDAC inhibitors for their ability to reverse changes in gene expression in cellular models.
authors.affiliation: Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Soragni
authors.forename: Chunping
authors.initials: C
authors.lastname: Xu
authors.forename: Andrew
authors.initials: A
authors.lastname: Cooper
authors.forename: Heather L
authors.initials: HL
authors.lastname: Plasterer
authors.forename: James R
authors.initials: JR
authors.lastname: Rusche
authors.forename: Joel M
authors.initials: JM
authors.lastname: Gottesfeld
mesh_terms: D000107:Acetylation / Q000187:drug effects; D015153:Blotting, Western; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation; D002843:Chromatin / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D005621:Friedreich Ataxia / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D020868:Gene Silencing / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D006655:Histone Deacetylases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D006816:Huntington Disease / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D033862:Iron-Binding Proteins / Q000235:genetics / Q000378:metabolism; D007753:Laboratories; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000096923:Frataxin
chemical_list: D002843:Chromatin; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases; D006657:Histones; D033862:Iron-Binding Proteins; D012333:RNA, Messenger; D000096923:Frataxin