ReviewCurrent medicinal chemistry2015
Unfolded Protein Response and PERK Kinase as a New Therapeutic Target in the Pathogenesis of Alzheimer's Disease.
Review in Current medicinal chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 68 citations in OpenAlex.
- The dual role of ATF4 in neurons: from stress adaptation to therapeutic intervention.Frontiers in molecular neuroscience · 2026Review
- Beneficial effects of food-medicine homologous herbs for patients with diabetic kidney disease.Frontiers in immunology · 2025Review
- Jiangu Recipe Suppresses ER Stress-induced Apoptosis and Inhibits Extracellular Matrix Degradation in Chondrocytes through Upregulating SIRT1 Expression.Current pharmaceutical biotechnology · 2025Article
- The role of glucagon-like peptide-1/GLP-1R and autophagy in diabetic cardiovascular disease.Pharmacological reports : PR · 2024Review
- The Unfolded Protein Response in a Murine Model of Alzheimer's Disease: Looking for Predictors.International journal of molecular sciences · 2023Article
- Exosomes Derived from M2 Microglial Cells Modulated by 1070-nm Light Improve Cognition in an Alzheimer's Disease Mouse Model.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Promoting Effect and Potential Mechanism ofFoods (Basel, Switzerland) · 2022Article
- 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
- Targeting NLRP3-Mediated Neuroinflammation in Alzheimer's Disease Treatment.International journal of molecular sciences · 2022Review
- Molecular origin of somatostatin-positive neuron vulnerability.Molecular psychiatry · 2022Article
- PERK activation by SB202190 ameliorates amyloidogenesis via the TFEB-induced autophagy-lysosomal pathway.Aging · 2022Article
- Article
- Hypoglycemia, Vascular Disease and Cognitive Dysfunction in Diabetes: Insights from Text Mining-Based Reconstruction and Bioinformatics Analysis of the Gene Networks.International journal of molecular sciences · 2021Article
- Genipin Attenuates Tau Phosphorylation and Aβ Levels in Cellular Models of Alzheimer's Disease.Molecular neurobiology · 2021Article
- Enhancing calmodulin binding to ryanodine receptor is crucial to limit neuronal cell loss in Alzheimer disease.Scientific reports · 2021Article
- Review
- Endoplasmic Reticulum Stress in Diabetic Nephrology: Regulation, Pathological Role, and Therapeutic Potential.Oxidative medicine and cellular longevity · 2021Review
- A multi-omics analysis reveals the unfolded protein response regulon and stress-induced resistance to folate-based antimetabolites.Nature communications · 2020Article
- Exercise training ameliorates cerebrovascular dysfunction in a murine model of Alzheimer's disease: role of the P2Y2 receptor and endoplasmic reticulum stress.American journal of physiology. Heart and circulatory physiology · 2020Article
- Epigallocatechin-3-Gallate (EGCG) Improves Cognitive Deficits Aggravated by an Obesogenic Diet Through Modulation of Unfolded Protein Response in APPswe/PS1dE9 Mice.Molecular neurobiology · 2020Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Recent evidence suggests that the development of Alzheimer's disease (AD) and related cognitive loss is due to mutations in the Amyloid Precursor Protein (APP) gene on chromosome 21 and increased activation of eukaryotic translation initiation factor-2α (eIF2α) phosphorylation. The high level of misfolded and unfolded proteins loading in Endoplasmic Reticulum (ER) lumen triggers ER stress and as a result Unfolded Protein Response (UPR) pathways are activated. Stress-dependent activation of the protein kinase RNA-like endoplasmic reticulum kinase (PERK) leads to the significant elevation of phospho-eIF2α. That attenuates general translation and, on the other hand, promotes the preferential synthesis of Activating Transcription Factor 4 (ATF4) and secretase β (BACE1) - a pivotal enzyme responsible for the initiation of the amyloidogenic pathway resulting in the generation of the amyloid β (Aβ) variant with high ability to form toxic senile plaques in AD brains. Moreover, excessive, long-term stress conditions may contribute to inducing neuronal death by apoptosis as a result of the overactivated expression of pro-apoptotic proteins via ATF4. These findings allow to infer that dysregulated translation, increased expression of BACE1 and ATF4, as a result of eIF2α phosphorylation, may be a major contributor to structural and functional neuronal loss resulting in memory impairment. Thus, blocking PERK-dependent eIF2α phosphorylation through specific, small-molecule PERK branch inhibitors seems to be a potential treatment strategy for AD individuals. That may contribute to the restoration of global translation rates and reduction of expression of ATF4 and BACE1. Hence, the treatment strategy can block accelerated β -amyloidogenesis by reduction in APP cleaving via the BACE1-dependent amyloidogenic pathway.
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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.