logo SBA

ETD

Archivio digitale delle tesi discusse presso l’Università di Pisa

Tesi etd-01082021-160030


Tipo di tesi
Tesi di laurea magistrale
Autore
RECUPERO, LUCA
URN
etd-01082021-160030
Titolo
Aβ oligomer treatment on human neocortical neurons reveals potential candidate targets in Alzheimer's disease
Dipartimento
BIOLOGIA
Corso di studi
NEUROSCIENCE
Relatori
relatore Prof. Onorati, Marco
relatore Dott.ssa Dell'Anno, Maria Teresa
Parole chiave
  • Alzheimer's disease
  • Amyloid beta oligomers
  • neural stem cells
Data inizio appello
26/01/2021
Consultabilità
Completa
Riassunto
Alzheimer's disease (AD) is one of the most common forms of dementia worldwide. Even though AD histopathological features have been largely described, the upstream causative agent of the disease is far from being entirely elucidated. According to the Amyloid Cascade Hypothesis, the generation of β-Amyloids (Aβ), forming oligomers (Aβo) and later plaques, is the primary pathological event in AD, leading to progressive neuronal injuries and ultimately dementia. The present work has focused on trying to shed light on the intracellular mechanisms related to Aβo toxicity. Conscious that the neocortex is one of the most damaged regions in AD brains, we generated human neocortical (NCX) neurons through the differentiation of neuroepithelial stem (NES) cells collected from the developing human forebrain. Mass spectrometry (MS) analysis has succeeded in identifying novel intracellular agents that appear to be altered in our neuronal cultures upon Aβo treatment. A substantial effort of the present thesis has been devoted to the validation of MS data, mostly through immunofluorescence assays, aimed at investigating the signaling cascade evoked by Aβo insult. Intriguingly, our results obtained from cultured neurons appear to be in agreement with preliminary observations of human brain sections from AD patients and age-matched controls. In conclusion, the present project revealed protein candidates whose phosphorylation appears to be modified in human NCX neurons after treatment with synthetic Aβo, a finding that may have an impact on the identification of novel biomarkers and potential targets for AD.
File