Genetika Parkinsonove bolesti

master's thesis

• Title (english): Genetics of Parkinson's disease
• Author: Mirna Majzec
• Mentor: Srđana Telarović (mentor)
• Committee member: Zdravka Poljaković-Skurić (predsjednik povjerenstva)
• Committee member: Tamara Nikuševa Martić (član povjerenstva)
• Committee member: Srđana Telarović (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Neurology); Zagreb
• Defense date and country: 2021-07-16, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Neurology

Abstract

Parkinsonova bolest druga je po redu najčešća neurodegenerativna bolest multifaktorijalne etiologije. Parkinsonova bolest tradicionalno se dijeli na monogenetski/ familijarni oblik Parkinsonove bolesti, te na idiopatski/ sporadični oblik Parkinsnove bolesti. Nastaje primarno kao posljedica propadanja dopaminergičkih neurona u kompaktnom dijelu crne tvari. Kao posljedica nedostatka dopamina javljaju se glavni motorički simptomi koji uključuju tremor u mirovanju, bradikinezu, posturalnu nestabilnost te rigidnost. Uz glavne motoričke simptome, u oboljelih javljaju se i nemotorički simptomi poput apatije, autonomnih poremećaja, depresije, demencije i poremećaja spavanja. Dijagnoza je Parkinsonove bolesti klinička. Osim genetskog testiranja u odabranim slučajevima, definitivna dijagnoza Parkinsonove bolesti može se utvrditi tek posmrtnim identificiranjem neuropatoloških promjena. Liječenje Parkinsonove bolesti za sad je samo simptomatsko, farmakološkim i kirurškim metodama. Parkinsonova bolest kompleksna je bolest za koju su identificirane česte i rijetke genetske varijante koje doprinose razvoju bolesti. Česte genetske varijante s visokom penetrantnosti dovode do nastanka monogenetskog oblika Parkinsonove bolesti. Mutacije koje uzrokuju monogenetski oblik, jedini su za sada poznati uzrok Parkinsonove bolesti. Rijetke genetske varijante smatraju se rizičnim faktorom za nastanak idiopatskog oblika Parkinsnove bolesti. Smatra se da za nastanak idiopatskog oblika Parkinsonove bolesti važnu ulogu imaju interakcije okolišnih i genetskih čimbenika. Razvojem tehnologije otkriva se sve veći broj genetskih rizičnih čimbenika. Istraživanja mutacija u monogenetskom obliku te otkrivanjem rizičnih genetskih varijanti u idiopatskom obliku omogućava bolje razumijevanje patogeneze Parkinsonove bolesti te čini važnu podlogu za razvoj terapije usmjerene na zaustavljanje progresije bolesti.

Abstract (english)

Parkinson's disease is the second most common neurodegenerative disease with multifactorial etiology. Parkinson's disease is traditionally classified as either monogenetic / familial Parkinson's disease or as idiopathic / sporadic Parkinson's disease. It primarily associated with a loss of dopaminergic neurons in the substantia nigra pars compact. Dopamine deficiency results in major motor symptoms that include resting tremor, bradykinesia, postural instability, and rigidity. In addition to the main motor symptoms, patients also exhibit non-motor symptoms such as apathy, autonomic disorders, depression, dementia, and sleep disorders. The diagnosis of Parkinson's disease is clinical. In addition to genetic testing in selected cases, a definitive diagnosis of Parkinson's disease can only be established by postmortem identification of neuropathological changes. The treatment of Parkinson's disease is currently only symptomatic, with both pharmacological and surgical methods applied. Parkinson's disease is a complex disease for which common and rare genetic variants have been identified that contribute to the development of the disease. Common genetic variants with high penetrance lead to the development of a monogenetic form of a disease. Genetic mutations that cause the monogenetic Parkinson's disease are the only currently known cause of a disease. Rare genetic variants are considered a risk factor for the development of idiopathic Parkinson's disease. Interactions of environmental and genetic factors are thought to play an important role in the development of the idiopathic form of a disease. With the development of new technologies, an increasing number of genetic risk factors are being discovered. Studies of mutations in monogenetic disease, and identification of new genetic variants associated with idiopathic Parkinson’s disease, provide a better understanding of the pathogenesis, and forms an important basis for the development of therapy aimed at stopping disease progression.

• Keywords: Parkinsonova bolest; monogenetski oblik Parkinsonove bolesti; genetski rizični čimbenici
• Keywords (english): Parkinson's disease; monogenetic Parkinson's disease; genetic risk factors
• Language: croatian
• URN:NBN: urn:nbn:hr:105:488454
• Study programme: Title: Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2022-03-11 09:02:45