Doctoral theses
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Identifier |
000369268 |
Title |
Διερεύνηση του προστατευτικού ρόλου του μονοπατίου απόκρισης σε θερμικό σοκ έναντι του νεκρωτικού κυτταρικού θανάτου στο νηματώδη Caenorhabditis elegans |
Alternative Title |
Study of the protective role of the heat shock response pathway against necrotic cell death in the nematode Caenorhabditis elegans |
Author
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Κούρτης, Νικόλαος
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Thesis advisor
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Ταβερναράκης, Νεκτάριος
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Abstract |
Necrotic cell death contributes to the pathogenesis of many
neurodegenerative diseases and other pathological situations. However, the molecular mechanisms underlying necrosis are not fully understood.
We find that activation of the heat shock response pathway by means of heat preconditioning strongly suppresses necrotic cell death triggered by extreme environmental conditions in a model of heat stroke in C. elegans. Heat preconditioning also ameliorates excitotoxic neuronal death as well as
necrosis caused by hypoxia, in C. elegans.
The heat shock response is a highly conserved gene expression
program, which is engaged under conditions of stress and coordinates expression of specific genes that protect cells against various stressors. Removal of the heat shock factor 1 (HSF-1), the master transcription regulator which orchestrates the heat shock response, abolishes the protective effect of heat preconditioning. By contrast, overexpression of HSF-1 suppresses
neurodegeneration.
While screening for potential mediators of the protective effect of heat preconditioning, we found that the small heat shock protein HSP-16.1 is both necessary and sufficient for protection against necrosis. HSP-16.1 exerts its protective effect by modulating calcium release from the Golgi apparatus.
Interestingly, the Golgi specific Ca2+ pump pmr-1 is required for heat preconditioning to elicit its protective effect. Loss of pmr-1 function abolishes the capacity of hsp-16.1 overexpression to protect against necrotic cell death.
Our findings suggest that intervention strategies based on selective
manipulation of the heat shock response may effectively counter excitotoxicity and neurodegeneration.
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Language |
Greek |
Subject |
Heat stroke |
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Necrosis |
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Neurodegeneration |
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Stress |
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Θερμοπληξία |
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Νέκρωση |
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Νευροεκφυλισμός |
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Στρες |
Issue date |
2011-11-03 |
Collection
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School/Department--School of Sciences and Engineering--Department of Biology--Doctoral theses
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Type of Work--Doctoral theses
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Permanent Link |
https://elocus.lib.uoc.gr//dlib/d/2/a/metadata-dlib-2s27ftvnaflfko3f5s26n3f6t2_1319614213.tkl
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Views |
314 |