Mehanizmi razvoja Alzheimerove bolesti

undergraduate thesis

• Title (english): Developmental mechanisms of Alzheimer’s disease
• Author: Iris Grgurina
• Mentor: Vesna Benković (mentor)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2018, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Alzheimerova bolest je kronična neurodegenerativna bolest s dobro definiranim
patofiziološkim mehanizmima koji najčešće utječu na područja medijalnog temporalnog režnja i
susjedne neokortikalne strukture. Ekstracelularni neuralni plakovi i inercelularni fibrili su
najpoznatije patološke značajke Alzheimerove bolesti, a nastaju zbog akumulacije amiloid β
peptida i citoskeletnih promjena koje proizlaze iz hiperfosforilacije i agregacije mikrotubul
vezujućeg tau proteina. Nakon originalno uspostavljene amiloidne teroije prema kojoj je amiloid
β bio glavni nositelj patologije AD istraživanjima je utvrđeno da tau protein svojom agregacijom
u oligomere i fibrile uvelike doprinosi progresiji same bolesti. Unatoč brojnim istraživanjima
patologije AD i dalje ostaje nepoznato zašto razvoj bolesti traje desetljećima prije pojave prvih
simptoma, no smatra se da bi tome mogao biti razlog smanjena sposobnost uklanjanja pogrešno
smotanih, oligomernih i agregiranih oblika tau proteina koji se nakupljaju starenjem. Nakon
neuspješnih terapijskih intervencija usmjerenih na amiloid β noviji lijekovi za cilj imaju
fosforilaciju i agregaciju tau proteina, te se još čekaju ishodi njihovih kliničkih studija. Također
od velike važnosti za projektiranje novih terapeutika je i točno razumijevanje mehanizama
kojima se toksični tau oligomeri šire kroz sinapsu.

Abstract (english)

Alzheimer's disease is a chronic neurodegenerative disease with well-defined
pathophysiological mechanisms that most often affect the medial temporal lobe and adjacent
neocortical structures. Extracellular neural plaques and intercellular fibrils are most common
pathological features of Alzheimer's disease, resulting from the accumulation of amyloid β
peptides and cytoskeletal changes resulting from hyperphosphorylation and aggregation of
microtubule binding tau protein. After the originally established amyloid theory according to
which amyloid β was the main bearer of AD pathology, was found that tau protein by its
aggregation into oligomers and fibrils greatly contributes to the progression of the disease as
well. Despite the numerous studies of AD pathology, it remains unknown why the development
of the disease lasts decades before the appearance of the first symptoms, but it is considered that
the reason could be diminished ability to remove misfolded, oligomeric and aggregated forms of
protein, which accumulate with age. Following unsuccessful therapeutic interventions that target
amyloid β, new drugs are aiming at phosphorylation and aggregation of tau protein but we are
still awaiting the outcomes of their clinical studies. In addition, the accurate understanding of the
mechanisms by which the toxic tau oligomers are spread through the synapse is of great
importance for the design of new therapies.

• Keywords: Alzheimerova bolest; mehanizmi razvoja
• Keywords (english): Alzheimer's disease; developmental mechanisms
• Language: croatian
• URN:NBN: urn:nbn:hr:217:870451
• Study programme: Title: Molecular Biology; Study programme type: university; Study level: undergraduate; Academic / professional title: sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) molekularne biologije (sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) molekularne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2018-10-01 11:00:18