DEVELOPMENT OF MOLECULAR PROBES ACTING ON aSYN/TUBULIN AND TAU/TUBULIN INTERACTION
type: CreativeWork
description: Microtubules (MTs) are ubiquitous structures playing many roles in all eukaryotic cell types from fungi to mammals mainly consisting of conserved α/β tubulin heterodimers. Neurons are an impressive example of cells in which the contribution of MTs is fundamental to achieve their sophisticated cell architecture and to sustain their functional complexity. A growing body of evidence indicates that microtubule defects are linked to neurodegenerative diseases, such as Parkinson’s Disease (PD). Several independent studies report a genome-wide crucial association with PD of single nucleotide polymorphisms in the MAPT locus, containing the gene coding for the Tau protein, a microtubule-binding protein that is predominantly expressed in neurons. The evidence of Tau pathology in PD is striking and contributes to neuronal dysfunction, impairment of axonal transport and cell death underlying PD. Recently another protein, α-Synuclein (αSyn), was put in the spotlight of various research groups since it was found aggregated in PD patients’ brains. αSyn, composed of 140 amino acids, is in fact deeply involved in PD, as i) it is the main component of Lewy bodies, which are well-known as the histopathological hallmark of PD and ii) the gene that encodes it, SCNA, is mutated in familial PD. Even though, lots of new information regarding both αSyn/tubulin and Tau/tubulin have been obtained, their relevance over neuronal dysfunction remains unclear. For these reasons, their interaction is set at the center of my research project. The first main aim of this PhD is the development of peptide based molecular probes able to modulate the Tau and α-Synuclein interaction with Tubulin. A library of peptides, both native and mutated sequences of αSyn, were synthesized and were used as molecular ‘tools’ for the conduction of in vitro experiments. The secondary structure of the peptides was characterized so to have a better idea of their possible activities during the in vitro experiments. Microsc…
abstract: Microtubules (MTs) are ubiquitous structures playing many roles in all eukaryotic cell types from fungi to mammals mainly consisting of conserved α/β tubulin heterodimers. Neurons are an impressive example of cells in which the contribution of MTs is fundamental to achieve their sophisticated cell architecture and to sustain their functional complexity. A growing body of evidence indicates that microtubule defects are linked to neurodegenerative diseases, such as Parkinson’s Disease (PD). Several independent studies report a genome-wide crucial association with PD of single nucleotide polymorphisms in the MAPT locus, containing the gene coding for the Tau protein, a microtubule-binding protein that is predominantly expressed in neurons. The evidence of Tau pathology in PD is striking and contributes to neuronal dysfunction, impairment of axonal transport and cell death underlying PD. Recently another protein, α-Synuclein (αSyn), was put in the spotlight of various research groups since it was found aggregated in PD patients’ brains. αSyn, composed of 140 amino acids, is in fact deeply involved in PD, as i) it is the main component of Lewy bodies, which are well-known as the histopathological hallmark of PD and ii) the gene that encodes it, SCNA, is mutated in familial PD. Even though, lots of new information regarding both αSyn/tubulin and Tau/tubulin have been obtained, their relevance over neuronal dysfunction remains unclear. For these reasons, their interaction is set at the center of my research project. The first main aim of this PhD is the development of peptide based molecular probes able to modulate the Tau and α-Synuclein interaction with Tubulin. A library of peptides, both native and mutated sequences of αSyn, were synthesized and were used as molecular ‘tools’ for the conduction of in vitro experiments. The secondary structure of the peptides was characterized so to have a better idea of their possible activities during the in vitro experiments. Microsc…
author: PEQINI, KALIROI
language: eng
keywords: Settore CHIM/06 - Chimica Organica
date published: 2023-07-11
date modified: 2026-07-27T20:19:12Z
provider: Università degli Studi di Milano
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Università degli Studi di Milano

PropertyValue
property ID: Handle
value: https://hdl.handle.net/2434/984949

PropertyValue
property ID: DOI
value: 10.13130/peqini-kaliroi_phd2023-07-11