Rallis, Andrew and Navarro, Juan A. and Rass, Mathias and Hu, Amelie and Birman, Serge and Schneuwly, Stephan and Therond, Pascal P. (2020) Hedgehog Signaling Modulates Glial Proteostasis and Lifespan. CELL REPORTS, 30 (8). 2627-+. ISSN 2211-1247,
Full text not available from this repository. (Request a copy)Abstract
The conserved Hedgehog signaling pathway has well-established roles in development. However, its function during adulthood remains largely unknown. Here, we investigated whether the Hedgehog signaling pathway is active during adult life in Drosophila melanogaster, and we uncovered a protective function for Hedgehog signaling in coordinating correct proteostasis in glial cells. Adult-specific depletion of Hedgehog reduces lifespan, locomotor activity, and dopaminergic neuron integrity. Conversely, increased expression of Hedgehog extends lifespan and improves fitness. Moreover, Hedgehog pathway activation in glia rescues the lifespan and age-associated defects of hedgehog mutants. The Hedgehog pathway regulates downstream chaperones, whose overexpression in glial cells was sufficient to rescue the shortened lifespan and proteostasis defects of hedgehog mutants. Finally, we demonstrate the protective ability of Hedgehog signaling in a Drosophila Alzheimer's disease model expressing human amyloid beta in the glia. Overall, we propose that Hedgehog signaling is requisite for lifespan determination and correct proteostasis in glial cells.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | STEM-CELL RENEWAL; SONIC HEDGEHOG; DROSOPHILA-MELANOGASTER; PATHWAY ACTIVATION; ALZHEIMERS-DISEASE; GENE-EXPRESSION; REACTIVE GLIA; BRAIN; NEURONS; MODEL; |
| Subjects: | 500 Science > 590 Zoological sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Zoologie > Entwicklungsbiologie (Prof. Dr. Stephan Schneuwly) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 30 Mar 2021 09:55 |
| Last Modified: | 30 Mar 2021 09:55 |
| URI: | https://pred.uni-regensburg.de/id/eprint/45072 |
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