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Title: Role of Telomerase in neuronal survival during aging
Other Titles: De rol van telomerase in neuronale overleving bij het verouderen
Authors: Iannilli, Francesca
Issue Date: 29-May-2012
Abstract: Normal 0 false false false MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman"; mso-ansi-language:#0400; mso-fareast-language:#0400; mso-bidi-language:#0400;}<span style="mso-ansi-language:EN-GB" lang="EN-GB"&gt; For most differentiated cells, thenatural accumulation of toxic molecules from oxidative metabolism leads tofunctional stasis, death and replacement. However, despite the abundance oftoxic metabolic by-products, neurons do not die, even when old, indicating thatthese cells use robust, even non-conventional, survival mechanisms. Wehypothesised that one such mechanism may involve Telomerase ReverseTranscriptase (TERT), which exerts an anti-apoptotic role on mitochondria incancer cells (Massard et al., 2006). Here, we show that, as neurons age,TERT undergoes nucleus-to-cytoplasm translocation, both <i style="mso-bidi-font-style:normal"&gt;in vivo and in vitro.Functionally, reductions in TERT levels lead to neuronal apoptosis, whereasincreased amounts of TERT protects neurons against oxidative metabolism.Moreover, the prevention of TERT nuclear export abolishes the resistance todeath. Mechanistically, different from cancer cells, cytoplasmic TERT inneurons does not associate with mitochondria but with the RNA granulescontaining the messenger RNA for the pro-survival cyclin kinase inhibitorp15INK4B. Upon a secondary (acute) stress, p15INK4B and TERT dissociate, andp15INK4B undergoes efficient translation. These data suggest that fullydifferentiated neurons use cytoplasmic TERT as a constitutive response to basalstress conditions by sequestering anti-stress mRNAs into translationally silentRNA granules that can be released for translation and protection upon thearrival of an additional stress stimulus. <span style="mso-ansi-language:EN-GB" lang="EN-GB"&gt; <span style="mso-ansi-language:EN-GB" lang="EN-GB"&gt; <span style="mso-ansi-language:EN-GB" lang="EN-GB"&gt;
Publication status: accepted
KU Leuven publication type: TH
Appears in Collections:Department of Human Genetics - miscellaneous
Laboratory of Neuronal Differentiation

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