Functional and Pathophysiological-morphological Correlates of Neurodegenerative Diseases

• Název práce v češtině: Funkční a patofyziologicko-morfologické koreláty neurodegenerativních onemocnění
• Název v anglickém jazyce: Functional and Pathophysiological-morphological Correlates of Neurodegenerative Diseases
• Klíčová slova: akumulace železa, barevná diskriminace, huntingtin, Huntingtonova nemoc, komplex dýchacího řetězce, kontrastní senzitivita, mutace C19orf12, neurodegenerace, neurodegenerace asociovaná s mitochondriálním membránovým proteinem, optická koherenční tomografie, parkinsonismus, tloušťka vrstvy nervových vláken sítnice, víceúrovňový proces
• Klíčová slova anglicky: C19orf12 mutation, color discrimination, contrast sensitivity, huntingtin, Huntington's disease, iron accumulation, mitochondrial membrane-protein associated neurodegeneration, multilevel process, neurodegeneration, optical coherence tomography, parkinsonism, respiratory chain complex, retinal nerve fiber layer thickness
• Akademický rok vypsání: 2014/2015
• Typ práce: disertační práce
• Jazyk práce: angličtina
• Ústav: Neurologická klinika 1. LF UK a VFN (11-00600)
• Vedoucí / školitel: prof. MUDr. Jan Roth, CSc.
• Řešitel: skrytý - zadáno a potvrzeno stud. odd.
• Datum přihlášení: 07.10.2014
• Datum zadání: 07.10.2014
• Datum potvrzení stud. oddělením: 07.10.2014
• Datum a čas obhajoby: 04.09.2023 13:00
• Místo konání obhajoby: Kateřinská 30, Praha 2, budova D5, NEURS1, P.30, Neurologická klinika, přízemí, seminární místnost
• Datum odevzdání elektronické podoby: 31.05.2023
• Datum proběhlé obhajoby: 04.09.2023
• Předmět: Obhajoba dizertační práce (B90002)
• Oponenti: doc. MUDr. Marek Baláž, Ph.D.

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Parker Jr, W. D., & Parks, J. K. (

Předběžná náplň práce

Tato dizertační práce vykresluje neurodegenerativní onemocnění jako víceúrovňový proces, popisuje různé koreláty na jednotlivých patofyziologických úrovních a prezentuje vybrané koreláty na příkladu Huntingtonovy nemoci a neurodegenerace asociované s mitochondriálním membránovým proteinem (MPAN). Pro tyto účely používá různé metodologické přístupy jako základní laboratorní výzkum, klinickou práci, zobrazování a vytvoření databáze s databázovými výstupy. Popisuje změny množství komplexu I a komplexu IV dýchacího řetězce v buňkách bukálního epitelu pacientů s Huntingtonovou nemocí. Demonstruje nedostatečnou diagnostickou sílu optické koherenční tomografie při použití jako biomarkeru u Huntingtonovy nemoci. Shrnuje různé fenotypy MPAN a potvrzuje asociaci mutace genu pro C19orf12 a poruchy zraku. Dále prezentuje dobře dokumentovaný připad pacienta s MPAN.

Předběžná náplň práce v anglickém jazyce

This doctoral thesis pictures neurodegenerative diseases as a multilevel process, describes various correlates on each pathophysiological level, and presents selected correlates in Huntington’s disease and mitochondrial membrane protein-associated neurodegeneration (MPAN). It uses various methodological approaches such as basic laboratory research, clinical work, imaging, database formation, and database summary. Changes in the amount of respiratory chain complex I and respiratory chain complex IV in buccal epithelial cells of Huntington’s disease patients are described. The insufficient power of optical coherence tomography as a biomarker in Huntington’s disease is demonstrated. Various phenotypes of MPAN are summarized, and an association between C19orf12 mutation and visual impairment is confirmed. A phenotype of a well-documented case of MPAN is presented.