Hedgehog signalling in lifespan determination and neuroprotection in Drosophila (HHneuro).
Final Report Abstract
The increase in our life expectancy is accompanied by a dramatic rise in age-related diseases, in particular neurodegenerative diseases such as Alzheimer's disease, which lead to increased mortality. The individual death of neuronal and glial cells in the brain, which can no longer be replaced, plays a key role in this. The mechanisms important for the survival of these cells are manifold and the significance of important signaling pathways in this process are still largely unknown. Many of the signaling pathways required during development, such as the Hedgehog (Hh) signaling pathway, are still active in the adult body, but their importance for cell viability has only been rudimentarily investigated, if at all. The aim of this project was to take a closer look at the significance of the Hedgehog signaling pathway for the adult brain in Drosophila melanogaster. Hh was specifically chosen because we could show that without Hh there is a significant decrease in the lifespan of the flies, associated with neuronal defects in the brain, whereas additional activation of Hh leads to a significant increase in lifespan. In the search for the molecular causes, we were able to demonstrate that chaperones are activated in glial cells by Hh, which play an important role in the folding of new proteins and in the prevention of protein aggregates in the cells. We were thus able to show that the influence of Hh on proteostasis in adult neurons and glial cells plays an important role in the functional integrity of the brain and in the survival and lifespan of adult animals.
Publications
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The role of Hh signalling in proteostasis in the adult Drosophila nervous system Abstract at the European Drosophila Neurofly conference 2018
Juan A. Navarro; Mathias Rass;rew Rallis; Laura Gizler; Pascal P. Thérond & Stephan Schneuwly
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Hedgehog signalling modulates lifespan determination and glial proteostasis Abstract and oral presentation at the European Drosophila Research Conference 2019
Andrew Rallis; Juan A. Navarro; Mathias Rass; Amélie Hu; Serge Birman; Stephan Schneuwly & Pascal P. Thérond
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Hedgehog Signaling Modulates Glial Proteostasis and Lifespan. Cell Reports, 30(8), 2627-2643.e5.
Rallis, Andrew; Navarro, Juan A.; Rass, Mathias; Hu, Amélie; Birman, Serge; Schneuwly, Stephan & Thérond, Pascal P.
