ArticleThe Journal of cell biology2004
ERK activation promotes neuronal degeneration predominantly through plasma membrane damage and independently of caspase-3.
Article in The Journal of cell biology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
What it found
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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.
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Who cites it
65 citing papers in PubMed, 152 citations in OpenAlex.
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- Molecular Frameworks for ERK1/2 Inhibition: Lessons from Synthetic and SAR Explorations.ACS omega · 2025Review
- Drofenine as a Kv2.1 inhibitor alleviated AD-like pathology in mice through AActa pharmaceutica Sinica. B · 2025Article
- Chemotherapeutic Potential of Chlorambucil-Platinum(IV) Prodrugs against Cisplatin-Resistant Colorectal Cancer Cells.International journal of molecular sciences · 2024Article
- Anticancer Effect of PtCancers · 2024Article
- Involvement of Glucosamine 6 Phosphate Isomerase 2 (GNPDA2) Overproduction in β-Amyloid- and Tau P301L-Driven Pathomechanisms.Biomolecules · 2024Article
- Mitochondrion-Mediated Cell Death through Erk1-Alox5 Independent of Caspase-9 Signaling.Cells · 2022Article
- Apoptotic Pathways and Alzheimer's Disease: Probing Therapeutic Potential.Neurochemical research · 2021Review
- Protective effects of peptide FK18 against neuro-excitotoxicity in SH-SY5Y cells.Experimental and therapeutic medicine · 2021Article
- Metabolic Role of PTEN in Insulin Signaling and Resistance.Cold Spring Harbor perspectives in medicine · 2020Review
- 3-Hydroxy-3-Methylglutaric Acid Impairs Redox and Energy Homeostasis, Mitochondrial Dynamics, and Endoplasmic Reticulum-Mitochondria Crosstalk in Rat Brain.Neurotoxicity research · 2020Article
- Rhes, a striatal-enriched protein, promotes mitophagy via Nix.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Controlling ERK Activation Dynamics in Mammary Epithelial Cells with Alternating Electric Fields through Microelectrodes.Nano letters · 2019Article
- Promotion of Peripheral Nerve Regeneration by Stimulation of the Extracellular Signal-Regulated Kinase (ERK) Pathway.Anatomical record (Hoboken, N.J. : 2007) · 2019Review
- Death-Associated Protein Kinase 1 Phosphorylation in Neuronal Cell Death and Neurodegenerative Disease.International journal of molecular sciences · 2019Review
- Cannabinoid Receptor Type 1 Agonist ACEA Improves Cognitive Deficit on STZ-Induced Neurotoxicity Through Apoptosis Pathway and NO Modulation.Neurotoxicity research · 2019Article
- Quantitative proteomic analyses of dynamic signalling events in cortical neurons undergoing excitotoxic cell death.Cell death & disease · 2019Article
- Glycine Administration Alters MAPK Signaling Pathways and Causes Neuronal Damage in Rat Brain: Putative Mechanisms Involved in the Neurological Dysfunction in Nonketotic Hyperglycinemia.Molecular neurobiology · 2018Article
- Yeast genetic interaction screen of human genes associated with amyotrophic lateral sclerosis: identification of MAP2K5 kinase as a potential drug target.Genome research · 2017Article
- Olfactory bulb neuroproteomics reveals a chronological perturbation of survival routes and a disruption of prohibitin complex during Alzheimer's disease progression.Scientific reports · 2017Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Our recent studies have shown that extracellular-regulated protein kinase (ERK) promotes cell death in cerebellar granule neurons (CGN) cultured in low potassium. Here we report that the "death" phenotypes of CGN after potassium withdrawal are heterogeneous, allowing the distinction between plasma membrane (PM)-, DNA-, and PM/DNA-damaged populations. These damaged neurons display nuclear condensation that precedes PM or DNA damage. Inhibition of ERK activation either by U0126 or by dominant-negative mitogen-activated protein kinase/ERK kinase (MEK) overexpression results in a dramatic reduction of PM damaged neurons and nuclear condensation. In contrast, overexpression of constitutively active MEK potentiates PM damage and nuclear condensation. ERK-promoted cellular damage is independent of caspase-3. Persistent active ERK translocates to the nucleus, whereas caspase-3 remains in the cytoplasm. Antioxidants that reduced ERK activation and PM damage showed no effect on caspase-3 activation or DNA damage. These data identify ERK as an important executor of neuronal damage involving a caspase-3-independent mechanism.
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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 Socratic graph.