Rapid initiation of cell cycle reentry processes protects neurons from amyloid-β toxicity
| Autor: | Astrid F. Feiten, Nikolas K. Haass, Esmeralda Paric, Yazi D. Ke, Yuanyuan Deng, Annika van Hummel, Gabriella Chan, Sook Wern Chua, Lars M. Ittner, Celine Heu, Julia van der Hoven, Thomas Fath, Stefania Ippati |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Programmed cell death
Cell Survival Transgene Endogeny Mice Transgenic 03 medical and health sciences Amyloid beta-Protein Precursor Mice 0302 clinical medicine Ubiquitin Alzheimer Disease Animals Humans 030304 developmental biology Neurons 0303 health sciences Multidisciplinary Amyloid beta-Peptides biology Cell Cycle Geminin Reentry Cell cycle Biological Sciences Cell biology Disease Models Animal nervous system Toxicity biology.protein Disease Susceptibility 030217 neurology & neurosurgery Biomarkers |
| Zdroj: | Proc Natl Acad Sci U S A |
| ISSN: | 1091-6490 |
| Popis: | Neurons are postmitotic cells. Reactivation of the cell cycle by neurons has been reported in Alzheimer’s disease (AD) brains and models. This gave rise to the hypothesis that reentering the cell cycle renders neurons vulnerable and thus contributes to AD pathogenesis. Here, we use the fluorescent ubiquitination-based cell cycle indicator (FUCCI) technology to monitor the cell cycle in live neurons. We found transient, self-limited cell cycle reentry activity in naive neurons, suggesting that their postmitotic state is a dynamic process. Furthermore, we observed a diverse response to oligomeric amyloid-β (oAβ) challenge; neurons without cell cycle reentry activity would undergo cell death without activating the FUCCI reporter, while neurons undergoing cell cycle reentry activity at the time of the oAβ challenge could maintain and increase FUCCI reporter signal and evade cell death. Accordingly, we observed marked neuronal FUCCI positivity in the brains of human mutant Aβ precursor protein transgenic (APP23) mice together with increased neuronal expression of the endogenous cell cycle control protein geminin in the brains of 3-mo-old APP23 mice and human AD brains. Taken together, our data challenge the current view on cell cycle in neurons and AD, suggesting that pathways active during early cell cycle reentry in neurons protect from Aβ toxicity. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|