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Identifier 000426424
Title DNA damage-induced inflammation in neurodegeneration
Alternative Title Ο ρόλος της φλεγμονής που προκύπτει από τη συσσώρευση γενετικών βλαβών στον νευροεκφυλισμό
Author Νενεδάκη, Ηλέκτρα Θ.
Thesis advisor Γαρίνης, Γιώργος
Γκιρτζιμανάκη, Κατερίνα
Abstract Microglia cells are the brain resident macrophages. Microglia promote phagocytic clearance, provide trophic support to ensure tissue repair, protect neurons and maintain brain homeostasis. In this study we used a monocyte/macrophage-specific Ercc1-/- mouse (Cx3cr1-Cre) to impair DNA repair in tissue resident macrophages. According to our mouse phenotype, cerebellar ataxia- like neuropathology, we focused our research in microglia. The purpose of this study is to examine whether microglia- specific DNA damage accumulation is enough to drive age- related neuropathology. DNA damage accumulation in microglia cells leads to cytoplasmic presence of damaged chromatin fragments. There are indications that chromatin fragments are transported in the cytoplasm through nucleophagy. Cytoplasmic DNA triggers microglia priming in a cell autonomous manner through type I IFN response. Furthermore, these chromatin fragments are secreted to the extracellular space through microglia derived exosomes. Type I IFN signaling in combination with exosomes lead to Purkinje cells apoptosis, effectively promoting neurodegeneration.
Language English
Subject Microglia
Γενετικές βλάβες
Issue date 2019-11-29
Collection   Faculty/Department--Faculty of Sciences and Engineering--Department of Biology--Post-graduate theses
  Type of Work--Post-graduate theses
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