ArticleBrain : a journal of neurology2017
Repurposed drugs targeting eIF2α-P-mediated translational repression prevent neurodegeneration in mice.
Article in Brain : a journal of neurology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 155 papers, 2 of them syntheses that pooled it.
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Who cites it
155 citing papers in PubMed, 2 syntheses or guidelines pooled it, 291 citations in OpenAlex.
- Pooled it
- The effects of trazodone on human cognition: a systematic review.European journal of clinical pharmacology · 2021Pooled it
- Efficacy of donepezil versus donepezil and trazodone in combination cognitive dysfunction in patients with dementia: a randomized controlled trial.Naunyn-Schmiedeberg's archives of pharmacology · 2026Trial
- Trial
- Genomic insights into the tunicamycin-induced endoplasmic reticulum stress response in peripheral blood mononuclear cells: A comprehensive RNA sequencing analysis.Biochemistry and biophysics reports · 2026Article
- Encephalopathy-linked UFM1 variants impede neuronal protein translation, development, and function.EMBO molecular medicine · 2026Article
- Neurons with granulovacuolar degeneration bodies are resilient to tau-induced protein synthesis impairment.Science advances · 2026Article
- Stress granules as a central hub linking organelle stress, aging, and neurodegeneration.BMB reports · 2026Review
- Adaptive inter-tissue proteostasis networks in aging and neurodegeneration.Bioscience reports · 2026Review
- Dysregulated mRNA Translation in Alzheimer's Disease: Mechanisms, Therapeutic Opportunities, and Challenges for Clinical Translation.Clinical interventions in aging · 2026Review
- Mutant Tau (P301L) Enhances Global Protein Translation in Differentiated SH-SY5Y Cells by Upregulating mTOR Signalling.International journal of molecular sciences · 2026Article
- Nucleophosmin supports WNT-driven hyperproliferation and tumor initiation.Nature genetics · 2026Article
- Unraveling Neurodegenerative Disorders: The Potential of Indole and Imidazole-Based Heterocycles.Current topics in medicinal chemistry · 2026Review
- GCN2 regulates paclitaxel-induced neuropathic pain.British journal of pharmacology · 2025Article
- Translational Remodeling of the Synaptic Proteome During Aging.Aging cell · 2025Article
- The Proteostasis Network in Proteinopathies: Mechanisms and Interconnections.The American journal of pathology · 2025Review
- Navigating the landscape of protein folding and proteostasis: from molecular chaperones to therapeutic innovations.Signal transduction and targeted therapy · 2025Review
- Inhibition of the Integrated Stress Response Prevents Natural Forgetting and Corrects Accelerated Forgetting Associated with Epilepsy.Molecular neurobiology · 2025Article
- Homeostasis control in health and disease by the unfolded protein response.Nature reviews. Molecular cell biology · 2025Review
- Article
95 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
See Mercado and Hetz (doi:10.1093/brain/awx107) for a scientific commentary on this article.Signalling through the PERK/eIF2α-P branch of the unfolded protein response plays a critical role in controlling protein synthesis rates in cells. This pathway is overactivated in brains of patients with Alzheimer's disease and related disorders and has recently emerged as a promising therapeutic target for these currently untreatable conditions. Thus, in mouse models of neurodegenerative disease, prolonged overactivation of PERK/eIF2α-P signalling causes sustained attenuation of protein synthesis, leading to memory impairment and neuronal loss. Re-establishing translation rates by inhibition of eIF2α-P activity, genetically or pharmacologically, restores memory and prevents neurodegeneration and extends survival. However, the experimental compounds used preclinically are unsuitable for use in humans, due to associated toxicity or poor pharmacokinetic properties. To discover compounds that have anti-eIF2α-P activity suitable for clinical use, we performed phenotypic screens on a NINDS small molecule library of 1040 drugs. We identified two compounds, trazodone hydrochloride and dibenzoylmethane, which reversed eIF2α-P-mediated translational attenuation
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.