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Identifier

000389102

Title

Molecular and genetic study of the multiple signaling pathways of the p75 neurotrophin receptor in schwann cells

Alternative Title

Μοριακή και γενετική μελέτη των πολλαπλών σηματοδοτικών μονοπατιών του υποδοχέα νευροτροφίνων p75 στα κύτταρα schwann

Author

Δεληβανόγλου, Νικολέτα

Thesis advisor

Χαραλαμπόπουλος, Ιωάννης

Abstract

The p75 death receptor is a pan-neurotrophin receptor, belongs to TNFR family and is expressed, both on neurons and glia, during development and adulthood and it can be induced after nerve injury or/and disease. It has been extensively described that p75NTR can mediate a variety of functions such as cell death, survival, axonal growth, proliferation and myelination. In addition, p75NTR binds to all neurotrophins and is the high-affinity receptor for the immature isoforms of neurotrophins (pro-neurotrophins). It can also bind other non neurotrophic ligands such as Aβ-amyloid, prion proteins (PrP) or myelin derived proteins such as myelinassociated glycoprotein (MAG). Due to lack of intrinsic enzymatic activity, it interacts with a plethora of intracellular proteins in order to activate different signaling cascades. In structure-function studies has been established that different ligands evoke different conformational changes of the receptor molecule that regulate differentially the cellular response. Understanding of its physiology, genetic and molecular biology may contribute to novel therapeutic approaches to malfunction of the nervous system in pathological conditions. In this study, we investigated the ligand-depended interaction between p75NTR and receptor-interacting protein 2 (RIP-2), an adaptor protein involved in cell survival in Schwann cells and we demonstrate the potential protective role of two novel p75NTR ligands, dehydroepiandrosterone (DHEA) and its synthetic analogue BNN27, in apoptosis.

Language

English

Subject

Apoptosis

Neurotrophin

Receptor-interacting protein

Schwann cells

p75 receptor

Issue date

2014-12-04

Collection

School/Department--School of Medicine--Department of Medicine--Post-graduate theses