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Review

Quercetin Regulates the Integrated Stress Response to Improve Memory

1
Department of Neurobiology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan
2
Department of Health and Nutritional Science, Nagoya University of Economics, Aichi 484-8504, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(11), 2761; https://doi.org/10.3390/ijms20112761
Received: 6 May 2019 / Revised: 2 June 2019 / Accepted: 3 June 2019 / Published: 5 June 2019
(This article belongs to the Special Issue Perspectives on the Health Benefits of Flavonoids)
The initiation of protein synthesis is suppressed under several stress conditions, inducing phosphorylation of the α-subunit of the eukaryotic initiation factor 2 (eIF2α), thereby inactivating the GTP-GDP recycling protein eIF2B. By contrast, the mammalian activating transcription factor 4 (ATF4, also known as cAMP response element binding protein 2 (CREB2)) is still translated under stress conditions. Four protein kinases (general control nonderepressible-2 (GCN2) kinase, double-stranded RNA-activated protein kinase (PKR), PKR-endoplasmic reticulum (ER)-related kinase (PERK), and heme-regulated inhibitor kinase (HRI)) phosphorylate eIF2α in the presence of stressors such as amino acid starvation, viral infection, ER stress, and heme deficiency. This signaling reaction is known as the integrated stress response (ISR). Here, we review ISR signaling in the brain in a mouse model of Alzheimer’s disease (AD). We propose that targeting ISR signaling with quercetin has therapeutic potential, because it suppresses amyloid-β (Aβ) production in vitro and prevents cognitive impairments in a mouse model of AD. View Full-Text
Keywords: GADD34; ATF4; amyloid-β; neurogenesis; Alzheimer’s disease GADD34; ATF4; amyloid-β; neurogenesis; Alzheimer’s disease
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MDPI and ACS Style

Nakagawa, T.; Ohta, K. Quercetin Regulates the Integrated Stress Response to Improve Memory. Int. J. Mol. Sci. 2019, 20, 2761. https://doi.org/10.3390/ijms20112761

AMA Style

Nakagawa T, Ohta K. Quercetin Regulates the Integrated Stress Response to Improve Memory. International Journal of Molecular Sciences. 2019; 20(11):2761. https://doi.org/10.3390/ijms20112761

Chicago/Turabian Style

Nakagawa, Toshiyuki, and Kazunori Ohta. 2019. "Quercetin Regulates the Integrated Stress Response to Improve Memory" International Journal of Molecular Sciences 20, no. 11: 2761. https://doi.org/10.3390/ijms20112761

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