Tau promotes oxidative stress-associated cycling neurons in S phase as a pro-survival mechanism : possible implication for Alzheimer’s disease
| Autor: | Marine Denechaud, Sarah Geurs, Thomas Comptdaer, Séverine Bégard, Alejandro Garcia-Núñez, Louis-Adrien Pechereau, Thomas Bouillet, Yannick Vermeiren, Peter P. De Deyn, Romain Perbet, Vincent Deramecourt, Claude-Alain Maurage, Michiel Vanderhaegen, Sebastiaan Vanuytven, Bruno Lefebvre, Elke Bogaert, Nicole Déglon, Thierry Voet, Morvane Colin, Luc Buée, Bart Dermaut, Marie-Christine Galas |
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| Jazyk: | angličtina |
| Rok vydání: | 2023 |
| Předmět: |
Pro-survival
Oxidative stress General Neuroscience Humans Mice Animals Alzheimer Disease/metabolism tau Proteins/metabolism S Phase Phosphorylation Oxidative Stress Neurons/metabolism Amyloid beta-Peptides/metabolism Alzheimer’s disease Cell cycle S phase Tau Medicine and Health Sciences Biology and Life Sciences Human medicine Alzheimer's disease |
| Zdroj: | Progress in neurobiology Progress in neurobiology 223 (2023) PROGRESS IN NEUROBIOLOGY Progress in neurobiology, 223 Progress in neurobiology, vol. 223, pp. 102386 |
| ISSN: | 0301-0082 1873-5118 |
| Popis: | Multiple lines of evidence have linked oxidative stress, tau pathology and neuronal cell cycle re-activation to Alzheimer's disease (AD). While a prevailing idea is that oxidative stress-induced neuronal cell cycle reactivation acts as an upstream trigger for pathological tau phosphorylation, others have identified tau as an inducer of cell cycle abnormalities in both mitotic and postmitotic conditions. In addition, nuclear hypophosphorylated tau has been identified as a key player in the DNA damage response to oxidative stress. Whether and to what extent these observations are causally linked remains unclear. Using immunofluorescence, fluorescence-activated nucleus sorting and single-nucleus sequencing, we report an oxidative stress-associated accumulation of nuclear hypophosphorylated tau in a subpopulation of cycling neurons confined in S phase in AD brains, near amyloid plaques. Tau downregulation in murine neurons revealed an essential role for tau to promote cell cycle progression to S phase and prevent apoptosis in response to oxidative stress. Our results suggest that tau holds oxidative stress-associated cycling neurons in S phase to escape cell death. Together, this study proposes a tau-dependent protective effect of neuronal cell cycle reactivation in AD brains and challenges the current view that the neuronal cell cycle is an early mediator of tau pathology. ispartof: Prog Neurobiol vol:223 pages:102386- ispartof: location:England status: published |
| Databáze: | OpenAIRE |
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