Huntingtonova choroba (Huntington´s disease, HD) je smrtelné dědičné neurodegenerativní onemocnění s nástupem projevů až v dospělosti. Onemocnění je způsobeno expanzí cytozin-adenin-guanin (CAG) repetic v genu pro protein huntingtin (Htt), který je exprimován ve většině tkání. HD je charakteristická především rozsáhlou degenerací buněk centrální nervové soustavy, ale mutace má velký dopad i na další orgány a tkáně. Mechanismy těchto změn nejsou stále dostatečně popsány. Jednou z nezbytných součástí výzkumu HD jsou zvířecí modely., Huntington's disease (HD) is a fatal inherited neurodegenerative disease with onset of symptoms in adulthood. The disease is caused by the expansion of CAG repeats in the gene for the huntingtin protein, which is expressed in most tissues. HD is characterized by extensive degeneration of the cells of the central nervous system, but the mutation has a large impact on other organs and tissues too. The mechanisms of these changes have not yet been adequately described. Animal models are one of the fundamental approaches in HD research., and Daniela Pallová ... [et al.].
Huntington’s disease (HD) is a demential, neurodegenerative inheritable disease affecting middle-aged patients. HD is characterized by uncontrolled choreiform movements, psychiatric symptoms and cognitive decline. Histopathological changes in HD brains reveal a considerable damage to basal ganglia, particularly affecting middle-sized spiny neurons from the caudate-putamen region. Neurochemical changes are specifically oriented to deplete GABAergic and cholinergic systems, while molecular alterations include an increased expression of CAG trinucleotide at exon 1 from the huntingtin (htt) gene, as well as aggregation of mutant htt. Although several hypotheses regarding the mechanisms by which neurotoxicity is triggered in HD brains have been suggested on the basis of experimental evidence, so far it remains not clear which of them are predominant or whether they are complementary. Recent experimental evidence through transgenic mice models reveal an interesting inter action between expanded CAG triplets, mutant htt, and the increase in toxic metabolites from the kynurenine pathway. Further evidence supports the assumption that different toxic mechanisms (i.e. excitotoxicity, energy metabolism impairment, inflammatory events, oxidative stress, etc.) are confluent and depend on each other. In this review we will briefly summarize some of those findings and propose a final integrative hypothesis for HD., V. Pérez-de la Cruz, A. Santamaría., and Obsahuje bibliografii a bibliografické odkazy