News Release

Stress granules control Alzheimer's gene transcripts and neuronal proteostasis

Peer-Reviewed Publication

Impact Journals LLC

Figure 6

image: Figure 6. Changes in RNA levels after the depletion of G3BP1 and G3BP2, and AS-treatment in SH-SY5Y. view more 

Credit: 2023 Sato et al.

“Determining the mechanism underlying RNA sequestration in [stress granules] [...] could represent a key goal in the discovery and development of suitable [Alzheimer’s disease] biomarkers and therapies.”

BUFFALO, NY- June 1, 2023 – A new research paper was published on the cover of Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 15, Issue 10, entitled, “Stress granules sequester Alzheimer’s disease-associated gene transcripts and regulate disease-related neuronal proteostasis.”

Environmental and physiological stresses can accelerate Alzheimer’s disease (AD) pathogenesis. Under stress, a cytoplasmic membraneless structure termed a stress granule (SG) is formed and is associated with various neurodegenerative disorders, including AD. SGs contain translationally arrested mRNAs, suggesting that impaired RNA metabolism in neurons causes AD progression; however, the underlying mechanism remains unclear. 

In this new study, researchers Kaoru Sato, Ken-ichi Takayama and Satoshi Inoue from Tokyo Metropolitan Institute for Geriatrics and Gerontology identified numerous mRNAs and long non-coding RNAs that are directly targeted by the SG core proteins G3BP1 and G3BP2. 

“In this study, we conducted a genome-wide investigation of the G3BP1- and G3BP2-bound RNAs using enhanced cross-linking and immunoprecipitation-sequencing (eCLIP-seq) in the human neuroblastoma (NB) cell line SH-SY5Y.”

G3BP1 and G3BP2 redundantly target RNAs before and after stress conditions. The researchers further identified RNAs within SGs, wherein AD-associated gene transcripts accumulated, suggesting that SGs can directly regulate AD development. Furthermore, gene-network analysis revealed a possible link between the sequestration of RNAs by SGs and the impairment of protein neurohomeostasis in AD brains. 

“Together, our study provides a comprehensive RNA regulatory mechanism involving SGs, which could be targeted therapeutically to slow AD progression mediated by SGs.”


Read the full study: DOI: 

Corresponding Author: Satoshi Inoue -

Keywords: stress granule, RNP granule, eCLIP-seq, G3BP, Alzheimer’s disease

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About Aging-US:

Launched in 2009, Aging (Aging-US) publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.

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