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Challenges of Huntington's disease and quest for therapeutic biomarkers
Author(s) -
Kotrcova Eva,
Jarkovska Karla,
Valekova Ivona,
Zizkova Martina,
Motlik Jan,
Gadher Suresh Jivan,
Kovarova Hana
Publication year - 2015
Publication title -
proteomics – clinical applications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.948
H-Index - 54
eISSN - 1862-8354
pISSN - 1862-8346
DOI - 10.1002/prca.201400073
Subject(s) - huntingtin , huntington's disease , biology , huntingtin protein , neurodegeneration , trinucleotide repeat expansion , proteomics , exon , oxidative stress , biomarker , microbiology and biotechnology , genetics , disease , gene , medicine , biochemistry , allele , pathology , mutant
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.