Title Alzheimerova bolest: patofiziologija i liječenje
Title (english) Alzheimer's disease: Pathophysiology and treatment
Author Dea Petrinčić
Mentor Željko Svedružić (mentor)
Committee member Rozi Andretić Waldowski (predsjednik povjerenstva)
Committee member Željka Minić (član povjerenstva)
Committee member Željko Svedružić (član povjerenstva)
Granter University of Rijeka (Faculty of Biotechnology and Drug Development) Rijeka
Defense date and country 2022-07-18, Croatia
Scientific / art field, discipline and subdiscipline BIOTECHNICAL SCIENCES Biotechnology
Abstract Alzheimerova bolest je multifaktorijalna neurodegenerativna bolest koja
uzrokuje 60-80% svih demencija. Glavna karakteristika je nakupljanje
beta-amiloidnih plakova i neurofibrilarnih vretena u kori mozga, koje dovodi
do progresivnog opadanja kognitivnih funkcija. Alzheimerova se bolest
javlja u 2 oblika, sporadičnom i nasljednom, koji se razlikuju prema uzroku
te prosječnoj dobi početka bolesti. Zbog kompleksnosti, molekularni se
mehanizam nastanka objašnjava mnogobrojnim hipotezama od kojih su
najučestalije: hipoteza amiloidne kaskade, Tau hipoteza, kolinergička
hipoteza, hipoteza oksidativnog stresa, hipoteza upale te hipoteza
dishomeostaze metala. Upravo su na kolinergičkoj hipotezi temeljeni
lijekovi koji rade na principu inhibicije kolinesteraze, a trenutno su odobrena
3 takva lijeka: Donepezil, Galantamin i Rivastigmin. Navedeni lijekovi
spadaju u lijekove koji tretiraju simptome zajedno s Memantinom koji
funkcionira kao antagonist NMDA receptora. Druga skupina odobrenih
lijekova jesu lijekovi koji odgađaju kliničko opadanje, a trenutno je odobren
samo imunoterapeutik Aducanumab, koji djeluje uklanjanjem Aβ plakova.
Potaknuti navedenim istraživanjima, znanstvenici se sve više okreću drugim
hipotezama molekularnog mehanizma nastanka, uzimajući ih kao osnovnu
metu terapije pa se osim beta-amiloida istražuju i tau protein te upala i
oksidativni stres. Ovaj završni rad detaljno pojašnjava povezanost
navedenih hipoteza s patofiziologijom Alzheimerove bolesti te izlaže
postojeće terapijske opcije u svrhu boljeg razumijevanja njihovih
mehanizama djelovanja, čime se postavljaju osnove na kojima se temelje
daljnja istraživanja ove bolesti.
Abstract (english) Alzheimer's disease is a multifactorial neurodegenerative disorder which
causes 60-80% of all dementia. Main characteristic is progressive cognitive
decline caused by accumulation of β-amyloid plaques and neurofibrillary
tangles in cerebral cortex. There are 2 types of Alzheimer's disease, familial
and sporadic with differences in cause and age of onset. Due to disease
complexity, Molecular pathogenesis of Alzheimer's Disease is desribed by
several hypothesis, with main ones being: β-amyloid hypothesis, Tau
hypothesis, cholinergic hypothesis, hypothesis of oxidative stress,
inflammation hypothesis and metal dishomeostasis hypothesis. One of
these hypothesis, cholinergic hypothesis has set the base for drugs that
work as cholinesterase inhibitors. There are currently 3 approved
cholinesterase inhibitors used in treatment of Alzheimer's disease:
Donepezil, Galantamine and Rivastigmine. Those medications together with
NMDA receptor agonist Memantine are classified as drugs that treat
symptoms of Alzheimer's disease. Other type of treatment used are drugs
that delay clinical decline, with currently only immunotherapeutic
Aducanumab being approved for use. Sucess of this drug that binds and
removes Aβ plaques encouraged scientist to study other hypothesis and use
their findings as a targets in future therapies. New research, therefore use
not only β-amyloid as their main target but also tau protein, inflammation
and oxidative stress. This thesis gives detailed description of the connection
between hypothesis and pathofiziology of AD and presents existing
therapeutic options with purpose of better understanding their mechanism
of action, all in order to set the foundation on which future research will be
based.
Keywords
Alzheimerova bolest
neurodegeneracija
beta-amiloidni protein
tau protein
neurofibrilarna vretena
inhibitori kolinesteraze
agonist NMDA receptora
imunoglobulin
Keywords (english)
Alzheimer's disease
neurodegenration
β-amyloid peptide
tau protein
neurofibrillary tangles
cholinesterase inhibitors
NMDA receptor agonist
immunoglobulin
Language croatian
URN:NBN urn:nbn:hr:193:546139
Study programme Title: Biotechnology and drug research Study programme type: university Study level: undergraduate Academic / professional title: sveučilišni/a prvostupnik/prvostupnica biotehnologije i istraživanja lijekova (sveučilišni/a prvostupnik/prvostupnica biotehnologije i istraživanja lijekova)
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Created on 2022-10-24 11:26:05