Mitochondrial stress disrupts insulin production in diabetes, but reversing the damage may restore β-cell function. Mitochondria are essential for generating the energy that fuels cells and enables th...

Expression of poly-GR in skeletal muscle causes ALS-like muscle atrophy and NMJ deficits by inducing ISR-mediated translation block and MuSK degradation. These autonomous muscular pathologies and corresponding motor deficits can be therapeutically reversed by targeting muscle with ISRIB or X-17.

The German scientist, in the running to win the Nobel Prize, believes that his experimental drug can rejuvenate the brain and reverse a multitude of diseases

I don’t want to believe... I need to know. Vol II No 34 288 links Curated The discovery of an ancient village could rewrite Indigenous his...

HNRNPD promotes radioresistance in nasopharyngeal carcinoma by enhancing stress granule assembly and sequestering GRAMD4 mRNA. This suppresses GRAMD4 translation and inhibits mitochondrial apoptosis. Targeting the integrated stress response with ISRIB restores GRAMD4 expression and sensitizes tumors to radiotherapy, revealing a translational control mechanism underlying radioresistance. ABSTRACT Radiotherapy resistance remains a major obstacle in nasopharyngeal carcinoma (NPC). Stress granules (SGs), dynamic cytoplasmic ribonucleoprotein condensates, have been linked to therapy resistance, but their role in NPC radioresistance remains unclear. Here, we show that SGs are key mediators of NPC radioresistance. Radioresistant NPC cells displayed markedly enhanced SG formation in a dose- and time-dependent manner, whereas pharmacological inhibition with ISRIB or genetic disruption of G3BP1 significantly sensitized cells to irradiation in vitro and in vivo. Integrated transcriptomic and proteomic analyses identified heterogeneous nuclear ribonucleoprotein D (HNRNPD) as a critical SG-associated RNA-binding protein upregulated in resistant cells and associated with poor prognosis. Functionally, HNRNPD promoted radioresistance by suppressing apoptosis, whereas its depletion restored radiosensitivity. Mechanistically, HNRNPD underwent RNA-dependent phase separation through its C-terminal intrinsically disordered region and interacted with G3BP1 to facilitate SG assembly. Irradiation promoted cytoplasmic accumulation of HNRNPD, while the p37 isoform preferentially bound G3BP1 and functionally drove SG formation. HNRNPD further bound GRAMD4 mRNA via its RRM1 domain and sequestered it in SG-associated compartments, thereby repressing GRAMD4 translation, suppressing mitochondrial apoptosis, and promoting survival. Restoration of GRAMD4 abrogated HNRNPD-induced radioresistance. Together, these findings establish the HNRNPD–SG–GRAMD4 axis as a key determinant of NPC radioresistance and a potential therapeutic target for radiosensitization.

Metabolic stress imposed by the tumor microenvironment (TME) promotes T cell dysfunction and limits antitumor immunity. Alicea Pauneto et al. demonstrate the hypoxia within the TME drives chronic acti...

The clinical utility of doxorubicin is limited by dose-dependent cardiotoxicity. Yang et al. identify an integrated stress response (ISR)-driven ATF4-METTL1-NLRP3 axis underlying this injury. ISRIB tr...

Yu et al. develop an engineered mesenchymal stem cell-liposome conjugate that homes to fibrotic lesions and releases ISRIB and NMN in response to reactive oxygen species. This platform regulates pathological integrated stress response activation, restores epithelial stress homeostasis, promotes tissue repair, and ameliorates pulmonary and liver fibrosis.

The integrated stress response (ISR) is a cellular defense mechanism activated under stress conditions. When the ISR is activated, it slows the produc…

Researchers say brain damage, thought to be irreversible, may be able to be repaired with a single treatment overnight.

【Eur J Pharmacol】<AbstractText>The integrated stress response (ISR) has been implicated in cognitive decline associated with ag...

In the new study, UCSF researchers showed rapid restorati...

In a groundbreaking study published in the Journal of Translational Medicine, researchers have unveiled a novel therapeutic approach that could significantly mitigate the effects of septic

Researchers found that faulty mitochondria in pancreatic cells trigger a stress response that disrupts insulin production, contributing to type 2 diabetes. The study also showed that ISRIB, an experim...