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Identifier

000426492

Title

The role of autophagy in proBDNF secretion under stress conditions

Alternative Title

Ο ρόλος της αυτοφαγίας στην έκκριση του proBDNF

Author

Ζώτα, Ιωάννα Γ.

Thesis advisor

Νικολετοπούλου, Βασιλική

Abstract

Autophagy is a highly conserved multistep catabolic process during which cellular constituents sequestered in double membrane-bound vesicles, termed autophagosomes, and delivered to the lysosomes for degradation. Apart from the well-established role of autophagy as a bulk process clearing the cell of superfluous molecules or contributing to cell response under stress conditions, it is increasingly appreciated that autophagy can serve specific functions in specialized cell types. In line with this notion, recent evidence suggests that autophagy facilitates unconventional secretion of the cytosolic cargo such as leaderless cytosolic proteins, and also affects conventional secretory pathways, including the constitutive and regulated secretion, as well as promotes alternative routes for trafficking of integral membrane proteins to the plasma membrane. Furthermore, several studies demonstrate that either overexpression or inhibition of autophagy mediators, dramatic alterations in the cellular secretory profile occur and secretion of a plethora of factors is affected. Encompassing a wide range of secreted factors, autophagy-mediated secretion is involved in diseases ranging from cancer to neurodegeneration. As refer to neurons, recent study revealed that BDNF, the major growth factor for the central nervous system (CNS) induce synaptic plasticity via suppressing autophagy, while other studies suggested autophagy activation by p75NTR, a receptor in which BDNF precursor (proBDNF) selectively binds. Thus, we decided to investigate the role of autophagy in proBDNF secretion under stress conditions and demonstrate if it is involved in autophagic flux induction. Our findings suggest that under nutrient deprivation proBDNF is unconventionally secreted via autophagosomes and it likely induces apoptosis in post synaptic cells via p75NTR activation. We also developed a viral construct for monitoring of autophagic flux in order to confirm our suggestion that apoptosis is mediated by autophagy induction.

Language

English

Subject

Aytophagosomes

Neurotrophins

Αυτοφαγοσώματα

Νευροτροφίνες

Issue date

2019-11-29

Collection

School/Department--School of Sciences and Engineering--Department of Biology--Post-graduate theses

Type of Work--Post-graduate theses