Quercetin Regulates the Integrated Stress Response to Improve Memory
Toshiyuki Nakagawa1, Kazunori Ohta2
1Department of Neurobiology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan. tnakagaw@gifu-u.ac.jp.
International Journal of Molecular Sciences
|June 15, 2019
Summary
The integrated stress response (ISR) pathway is activated by cellular stress, impacting protein synthesis. Targeting ISR with quercetin shows promise for Alzheimer
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- Protein synthesis initiation is suppressed under stress via eukaryotic initiation factor 2 alpha (eIF2α) phosphorylation.
- This inactivation of eIF2B occurs during the integrated stress response (ISR), mediated by four kinases (GCN2, PKR, PERK, HRI).
- Mammalian activating transcription factor 4 (ATF4) translation persists under stress conditions.
Purpose of the Study:
- To review integrated stress response (ISR) signaling in the brain.
- To investigate the therapeutic potential of targeting ISR in a mouse model of Alzheimer's disease (AD).
Main Methods:
- Review of ISR signaling mechanisms.
- In vitro studies on amyloid-beta (Aβ) production.
- Assessment of cognitive function in a mouse model of AD.
Main Results:
- Quercetin suppresses amyloid-beta (Aβ) production in vitro.
- Quercetin prevents cognitive impairments in a mouse model of AD.
- ISR signaling is implicated in AD pathogenesis.
Conclusions:
- Targeting ISR signaling represents a potential therapeutic strategy for Alzheimer's disease.
- Quercetin demonstrates efficacy in reducing AD pathology and cognitive deficits in preclinical models.
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