title: Targeting mutant huntingtin for the development of disease-modifying therapy.
abstract: Huntington's disease (HD) is a progressive and fatal neurodegenerative disease, and the most common inherited CAG repeat disorder. A polyglutamine expansion in the N-terminus of the huntingtin protein (HTT) leads to protein misfolding and downstream pathogenic processes culminating in widespread functional impairment and neurodegeneration in the striatum, cortex and other brain areas. To date, only symptomatic treatments are available that address motor, psychiatric and cognitive deficits. Here we review recent strategies for developing disease-modifying therapies designed to limit or abolish the pathogenic activities of the primary molecular target in HD, the mutant HTT protein itself.
authors: Abbott Laboratories, Neuroscience Discovery, Ludwigshafen, Germany.
authors: Thomas
authors: T
authors: Appl
authors: Linda
authors: L
authors: Kaltenbach
authors: Donald C
authors: DC
authors: Lo
authors: Georg C
authors: GC
authors: Terstappen
mesh_terms: D000818:Animals; D001921:Brain / Q000503:physiopathology; D003072:Cognition Disorders / Q000188:drug therapy / Q000209:etiology; D015195:Drug Design; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D058990:Molecular Targeted Therapy; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D017510:Protein Folding
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins