ReviewBiomolecules2021
PERK Pathway and Neurodegenerative Disease: To Inhibit or to Activate?
Review in Biomolecules, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
What it found
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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
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
- Molecular mechanisms of programmed cell death in methamphetamine-induced neuronal damage.Frontiers in pharmacology · 2022Pooled it
- Neuroinflammatory and molecular pathways in Alzheimer's disease: mechanistic crosstalk and emerging therapeutic opportunities.Inflammopharmacology · 2026Review
- Differential Sensitivity of HSV-1 and PRV to IFN-λ Reveals a Neuron-Specific Antiviral Role for RSAD2.bioRxiv : the preprint server for biology · 2026Article
- The endoplasmic reticulum in mitochondrial protein targeting: A neuronal perspective on organelle crosstalk.Protein science : a publication of the Protein Society · 2026Review
- Expression and role of HSPA5 in environmental toxin-induced neurological disorders.Frontiers in molecular neuroscience · 2026Review
- Parthenolide Exerts Protection against Hypoxic-Ischemic Brain Damage in Neonatal Rats by Inhibiting Perk-Mediated Endoplasmic Reticulum Stress.Molecular neurobiology · 2025Article
- ER stress tolerance is regulated by copper-dependent PERK kinase activity.Cell reports · 2025Article
- ER stress and/or ER-phagy in drug resistance? Three coincidences are proof.Cell communication and signaling : CCS · 2025Review
- Kinome screening identifies integrated stress response kinase EIF2AK1/HRI as a negative regulator of PINK1 mitophagy signaling.Science advances · 2025Article
- Methylglyoxal Formation-Metabolic Routes and Consequences.Antioxidants (Basel, Switzerland) · 2025Review
- Article
- ER stress sensors at the ER-mitochondrial interface, controlling mitochondrial health in neurodegenerative diseases.Frontiers in neuroscience · 2025Review
- Article
- Stress Induced Mitochondrial Hyperfusion (SIMH): A Concise Review on SIMH in Neurodegenerative Disorders and Other Diseases.Organelle (Tucson, Ariz.) · 2025Article
- Endoplasmic Reticulum-Targeting Natural Compounds: A Novel Frontier in Alleviating Liver Fibrosis.Drug design, development and therapy · 2025Review
- Exploring Endocannabinoid System: Unveiling New Roles in Modulating ER Stress.Antioxidants (Basel, Switzerland) · 2024Review
- Potential Role of Endoplasmic Reticulum Stress in Modulating Protein Homeostasis in Oligodendrocytes to Improve White Matter Injury in Preterm Infants.Molecular neurobiology · 2024Review
- IRE1/JNK Is the Leading UPR Pathway in 6-OHDA-Induced Degeneration of Differentiated SH-SY5Y Cells.International journal of molecular sciences · 2024Article
- Review
- Insights into the Activation of Unfolded Protein Response Mechanism during Coronavirus Infection.Current issues in molecular biology · 2024Review
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
Abstract
With the extension of life span in recent decades, there is an increasing burden of late-onset neurodegenerative diseases, for which effective treatments are lacking. Neurodegenerative diseases include the widespread Alzheimer's disease (AD) and Parkinson's disease (PD), the less frequent Huntington's disease (HD) and Amyotrophic Lateral Sclerosis (ALS) and also rare early-onset diseases linked to mutations that cause protein aggregation or loss of function in genes that maintain protein homeostasis. The difficulties in applying gene therapy approaches to tackle these diseases is drawing increasing attention to strategies that aim to inhibit cellular toxicity and restore homeostasis by intervening in cellular pathways. These include the unfolded protein response (UPR), activated in response to endoplasmic reticulum (ER) stress, a cellular affliction that is shared by these diseases. Special focus is turned to the PKR-like ER kinase (PERK) pathway of the UPR as a target for intervention. However, the complexity of the pathway and its ability to promote cell survival or death, depending on ER stress resolution, has led to some confusion in conflicting studies. Both inhibition and activation of the PERK pathway have been reported to be beneficial in disease models, although there are also some reports where they are counterproductive. Although with the current knowledge a definitive answer cannot be given on whether it is better to activate or to inhibit the pathway, the most encouraging strategies appear to rely on boosting some steps without compromising downstream recovery.
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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.