Small molecule cognitive enhancer reverses age-related memory decline in mice
Elma S Frias,
Posted 15 Apr 2020
bioRxiv DOI: 10.1101/2020.04.13.039677
Posted 15 Apr 2020
With increased life expectancy age-associated cognitive decline becomes a growing concern, even in the absence of recognizable neurodegenerative disease. The integrated stress response (ISR) is activated during aging and contributes to age-related brain phenotypes. We demonstrate that treatment with the drug-like small-molecule ISR inhibitor ISRIB reverses ISR activation in the brain, as indicated by decreased levels of activating transcription factor 4 (ATF4) and phosphorylated eukaryotic translation initiation factor eIF2. Furthermore, ISRIB treatment reverses spatial memory deficits and ameliorates working memory in old mice. At the cellular level in the hippocampus, ISR inhibition i) rescues intrinsic neuronal electrophysiological properties, ii) restores spine density and iii) reduces immune profiles, specifically interferon and T cell-mediated responses. Thus, pharmacological interference with the ISR emerges as a promising intervention strategy for combating age-related cognitive decline in otherwise healthy individuals. ONE SENTENCE SUMMARY Inhibition of the integrated stress response restores neuronal and immune dysfunction and alleviates memory deficits in aged mice. ### Competing Interest Statement SB is an employee of Praxis Biotech. SB, GU and LD work at Fundacion Ciencia & Vida and receive partial funding from Praxis Biotech. P.W. is an inventor on U.S. Patent 9708247 held by the Regents of the University of California that describes ISRIB and its analogs. Rights to the invention have been licensed by UCSF to Calico. P.W. is a consultant for Praxis Biotech LLC and Black Belt TX Limited. The authors declare no other competing interests.
- Downloaded 433 times
- Download rankings, all-time:
- Site-wide: 44,704 out of 103,851
- In neuroscience: 7,706 out of 18,385
- Year to date:
- Site-wide: 10,642 out of 103,851
- Since beginning of last month:
- Site-wide: 20,690 out of 103,851
Downloads over time
Distribution of downloads per paper, site-wide
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!