Stress-induced nucleocytoplasmic shuttling of TDP-43 is controlled by eIF-5A hypusination
Poster Feb 13, 2017
Carlos Osorno, Shayna Smeltzer, Frank Zamudio, Zain Quadri, Maj-Linda Selenica
Aggregation and phosphorylation of TAR DNA-binding protein-43, TDP-43, has been found to be associated with the neuropathology of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTLD). It has been proposed that TDP-43 accumulation in stress granules (SG) may contribute to the aggregation of TDP43. Eukaryotic translational initiation factor 5A (eIF5A) is hypusinated by deoxyhypusine synthase (DHS) and deoxyhypusine hydroxylase (DOHH). It is involved at the level of mRNA turnover, cell proliferation, and protein translational elongation. In this experiment we sought to determine the function of hypusinated eIF5a in relation to TDP-43 pathology in nuclear and cytoplasmic compartments under cellular stress.
Early life stress (ELS) is highly associated with development of psychopathology
and mood disorders in adulthood. Genetic studies have identified variation in the gene calcium voltage-gated channel subunit alpha1C (CACNA1C) to increase risk for several psychiatric disorders. This poster assessed the expression of Cacna1c following prepubertal stress.
We found a distinct subpopulation of Tregs within BMSCs. Tregs and BMSCs in co-culture conferred neuroprotection that varied in a dose-dependent manner. Tregs minimized stem cell production of IL-6, a pro-inflammatory cytokine, and inhibited BMSC secretion of FGF-beta, a cytokine related to BMSC proliferation and differentiation. The ratio of Tregs found natively in BMSCs is optimally adapted to provide the maximum neuroprotective benefit of stem cell treatment after ischemic stroke.READ MORE