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Identifier

000376383

Title

The implication of proteasomal degradation in aging and neurodegeneration.Investigation of the protective role of the heat shock response against necrotic cell death

Alternative Title

Η συμμετοχή της πρωτεοσωμικής αποικοδόμησης στη γήρανση και τον νευροεκφυλισμό. Μελέτη της προστατευτικής δράσης της απόκρισης σε θερμικό σοκ στο νεκροτικό κυτταρικό θάνατο

Author

Georgila, Konstantina I

Author

Γεωργίλα, Κωνσταντίνα Ιωάννης

Thesis advisor

Ταβερναράκης, Νεκτάριος

Abstract

Preservation of cellular protein homeostasis (proteostasis) is of critical importance. The cell employs various mechanisms to achieve this. The main machinery for the degradation of long-lived 5 Georgila K. Master thesis or damaged proteins is the proteasome. We exploited the simple model organism Caenorhabditis elegans to examine whether enhancement of the proteasome activity, via overexpression of the core, rate-limiting proteasomal subunit, pbs-5 can act beneficially on the lifespan of the nematode. C. elegans’ lifespan is regulated by several conserved and well characterized pathways. We aim to investigate, by genetic analysis, whether increased protein turnover confers lifespan extension by acting through those pathways. In addition, we examined whether pbs-5 overexpression and consequently increased proteasomal degradation confers oxidative stress resistance. Finally, there is a striking connection between aging and the onset of many neurodegenerative disorders. We took advantage of an established model of neurodegeneration in C. elegans. We examined whether enhancement of the main cellular degradation machinery may lead to suppression of neurodegeneration. Understanding the mechanism by which preservation of cellular proteostasis, via enhancement of the proteasomal activity, extends lifespan, confers oxidative stress resistance and suppresses neurodegeneration may lead to new anti-aging strategies and therapeutic interventions. 1. INTRODUCTION

Language

Greek

Subject

Aging

Biochemisty

Heat shock

Necrotic cell death

Neurodegeneration

Proteasome

Γήρανση

Νευροεκφυλισμός

Issue date