The effect of Tau protein expression on neuroligin-1-mediated synaptic plasticity in a cell model of Alzheimer's disease

master's thesis

• Title (croatian): Utjecaj ekspresije proteina Tau na sinaptičku plastičnost posredovanu neuroliginom-1 u staničnom modelu Alzheimerove bolesti
• Author: Kamelija Horvatović
• Mentor: Susanne Wegmann (mentor)
• Mentor: Dubravka Hranilović (komentor)
• Committee member: Dubravka Hranilović (predsjednik povjerenstva)
• Committee member: Julija Erhardt (član povjerenstva)
• Committee member: Maja Matulić (član povjerenstva)
• Committee member: Dunja Leljak-Levanić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2023-09-29, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Alzheimer's disease (AD) is a progressive, neurodegenerative disorder characterized by the accumulation
of Tau neurofibrillary tangles that correlate with cognitive and memory decline. Synaptic dysfunction and
disruption of synaptic plasticity are among the earliest changes observed in the brains of patients and animal
models of AD. Recent evidence suggests a potential role for neuroligin-1 during the initial stages of AD in
the hippocampus. Neuroligin-1 is a postsynaptic adhesion molecule with a key role in stabilizing glutamatemediated long-term potentiation (LP) and memory formation. Despite the overlapping mechanisms, the
pathological influence of Tau protein on neuroligin-1 is not yet known. The aim of this work is to investigate
whether there is a direct relationship between the change in Tau protein expression and the level of
expression and function changes of neuroligin-1. This pilot study implies that the overexpression of Tau
protein and increased Tau phosphorylation at serine residue Ser262 are related to disruption in neuroligin1 levels in hippocampal neurons, providing valuable insight into their potential roles and interaction in early
AD pathogenesis.

Abstract (croatian)

Alzheimerova bolest (AB) je progresivan, neurodegenerativni poremećaj karakteriziran nakupljanjem Tau
neurofibrilarnih snopića koji koreliraju s padom kognicije i memorije. Sinaptička disfunkcija i poremećaj
sinaptičke plastičnosti su među najranijim promjenama primijećenim u mozgu oboljelih i animalnim
modelima AB. Nedavni dokazi ukazuju na potencijalnu ulogu neuroligina-1 tijekom početnih stadija AB u
hipokampusu. Neuroligin-1 je postsinaptička adhezijska molekula s ključnom ulogom u stabilizaciji
dugotrajnog potenciranja (DP) posredovanog glutamatom i formiranju pamćenja. Unatoč preklapajućim
mehanizmima, još nije poznat patološki utjecaj proteina Tau na neuroligin-1. Cilj ovog rada je istražiti
postoji li direktna povezanost između promjene ekspresije proteina Tau i promjena razina ekspresije i
funkcije neuroligina-1. Ovo pilot istraživanje ukazuje na povezanost između povećane ekspresije proteina
Tau, hiperfosforilacije proteina Tau na serinskom ostatku Ser262 i poremećenih razina neuroligina-1 u
hipokampalnim neuronima, pružajući uvid u njihovu potencijalnu ulogu i interakciju u patogenezi ranog
stadija AB.

• Keywords: Hippocampus; neurodegeneration; synaptic dysfunction
• Keywords (english): Hipokampus; neurodegeneracija; sinaptička disfunkcija
• Language: english
• URN:NBN: urn:nbn:hr:217:301715
• Study programme: Title: Molecular Biology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra molekularne biologije (magistar/magistra molekularne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Embargoed access; Embargo expiration date: 2025-09-29
• Created on: 2023-11-15 12:23:28