ReviewMetabolic brain disease2020
Pathogenesis and promising therapeutics of Alzheimer disease through eIF2α pathway and correspondent kinases.
Review in Metabolic brain disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 26 citations in OpenAlex.
- Distinct cell type-specific mechanisms underlie cognitive dysfunction during persistent integrated stress response activation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Pathological Calcium Signaling in Traumatic Brain Injury and Alzheimer's Disease: From Acute Neuronal Injury to Chronic Neurodegeneration.International journal of molecular sciences · 2025Review
- Unlocking NAC's potential ATF4 and m6A dynamics in rescuing cognitive impairments in PTSD.Metabolic brain disease · 2025Article
- Screening and experimental validation of modified Gandou Decoction-targeted inhibitors for alleviating AD components via network pharmacology, machine learning, and molecular dynamics simulation.Frontiers in pharmacology · 2025Article
- Transcriptome and Animal Model Integration Reveals Inhibition of Calcium Homeostasis-Associated Gene ITPKB Alleviates Amyloid Plaque Deposition.Journal of molecular neuroscience : MN · 2024Article
- Bioinformatic analysis of hippocampal histopathology in Alzheimer's disease and the therapeutic effects of active components of traditional Chinese medicine.Frontiers in pharmacology · 2024Article
- The GCN2/eIF2αK stress kinase regulates PP1 to ensure mitotic fidelity.EMBO reports · 2023Article
- Melatonin: a promising neuroprotective agent for cerebral ischemia-reperfusion injury.Frontiers in aging neuroscience · 2023Review
- Protein synthesis inhibition and loss of homeostatic functions in astrocytes from an Alzheimer's disease mouse model: a role for ER-mitochondria interaction.Cell death & disease · 2022Article
- Review
- Targeting the Unfolded Protein Response as a Disease-Modifying Pathway in Dementia.International journal of molecular sciences · 2022Review
- A genetic link between risk for Alzheimer's disease and severe COVID-19 outcomes via the OAS1 gene.Brain : a journal of neurology · 2021Article
- Roles and Mechanisms of the Protein Quality Control System in Alzheimer's Disease.International journal of molecular sciences · 2021Review
- The PKR/P38/RIPK1 Signaling Pathway as a Therapeutic Target in Alzheimer's Disease.International journal of molecular sciences · 2021Review
- Remodelling of Cellular Protein Homeostasis by Enhanced ER-Mitochondrial Tethering.Contact (Thousand Oaks (Ventura County, Calif.))Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Eukaryotic initiation factor 2 (eIF2α) pathway is overactivated in Alzheimer disease and is probably associated with synaptic and memory deficiencies. EIF2α protein is principally in charge of the regulation of protein synthesis in eukaryotic cells. Four kinases responsible for eIF2α phosphorylation at ser-51 are: General control non-derepressible-2 kinase (GCN2), double-stranded RNA-activated protein kinase (PKR), PKR-like endoplasmic reticulum kinase (PERK), and heme-regulated inhibitor kinase (HRI) are the four kinases. They lead to reduced levels of general translation and paradoxical increase of stress-responsive mRNAs expression including the B-secretase (BACE1) and the transcriptional modulator activating transcription factor 4 (ATF4), which in turn accelerates the beta-amyloidogenesis, tau phosphorylation, proapoptotic pathway induction and autophagy elements formation leading to the main pathological hallmarks of AD. Findings suggest that genetic or pharmacological inhibition of correspondent kinases can restore memory and prevent neurodegeneration. This implies that inhibition of eIF2α phosphorylation through respondent kinases is indeed a feasible prospect of clinical application. This review discusses recent therapeutic approaches targeting eIF2α pathway and provides an overview of the links between correspondent kinases overactivation with neurodegeneration in AD.
Indexed as
Identifiers
What OpenQuestion holds
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.