title: Challenges of Huntington's disease and quest for therapeutic biomarkers.
abstract: Huntington's disease (HD) is the most common inherited neurodegenerative disorder among polyglutamine (polyQ) diseases caused by cytosine-adenine-guanine repeat expansion in exon 1 of the huntingtin gene whose translation results in polyQ stretch in the N-terminus of the huntingtin protein (HD protein). This mutation significantly affects huntingtin conformation, proteolysis, PTMs, as well as its ability to bind interacting proteins. As a consequence, a variety of cellular mechanisms such as transcription, mitochondrial energy metabolism, axonal transport, neuronal vulnerability to oxidative stress, neurotransmission, and immune response are altered and involved in the pathogenesis of HD. Promising candidate molecular biomarkers of HD have emerged from proteomic studies. Recent analyses focused on HD protein itself, its PTM, and interacting proteins, which are of great importance for disease course. Furthermore, brain, body fluids, and immune system are intensively studied in order to search for additional proteins with a view to their use as a biomarker(s) or set of biomarkers in clinical trials in HD translational research.
authors.affiliation: Institute of Animal Physiology and Genetics, Academy of Sciences of the Czech Republic, Libechov, Czech Republic; Research Center PIGMOD, Libechov, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Kotrcova
authors.forename: Karla
authors.initials: K
authors.lastname: Jarkovska
authors.forename: Ivona
authors.initials: I
authors.lastname: Valekova
authors.forename: Martina
authors.initials: M
authors.lastname: Zizkova
authors.forename: Jan
authors.initials: J
authors.lastname: Motlik
authors.forename: Suresh Jivan
authors.initials: SJ
authors.lastname: Gadher
authors.forename: Hana
authors.initials: H
authors.lastname: Kovarova
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism* / Q000628:therapy*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D020543:Proteome / Q000032:analysis*; D040901:Proteomics / Q000379:methods*
chemical_list: D015415:Biomarkers; D009419:Nerve Tissue Proteins; D020543:Proteome
keywords: HD biomarkers; Huntingtin neurotoxicity; Huntingtin pathogenesis; Huntington's disease