ArticleThe American journal of pathology2004
Calpain mediates calcium-induced activation of the erk1,2 MAPK pathway and cytoskeletal phosphorylation in neurons: relevance to Alzheimer's disease.
Article in The American journal of pathology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 1 of them a synthesis that pooled it.
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Who cites it
64 citing papers in PubMed, 1 synthesis or guideline pooled it, 124 citations in OpenAlex.
- Calpain Inhibitors as Potential Therapeutic Modulators in Neurodegenerative Diseases.Neurochemical research · 2022Pooled it
- Neuronal Calcium Signaling and Cytoskeletal Dynamics in Neurodegeneration.International journal of molecular sciences · 2026Review
- Pathological Calcium Signaling in Traumatic Brain Injury and Alzheimer's Disease: From Acute Neuronal Injury to Chronic Neurodegeneration.International journal of molecular sciences · 2025Review
- Oligodendrocyte-astrocyte crosstalk in Parkinson's disease mediates neuronal ferroptosis via the FGF signaling pathway.NPJ Parkinson's disease · 2025Article
- Hippocampal mitochondrial CaSaudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2023Article
- Vascular endothelial growth factor isoforms differentially protect neurons against neurotoxic events associated with Alzheimer's disease.Frontiers in molecular neuroscience · 2023Article
- Axonal transport of late endosomes and amphisomes is selectively modulated by local CaScience advances · 2022Article
- Viscoelastic Response of Neurofilaments: An Atomistic Simulation Approach.Biomolecules · 2021Article
- Article
- Probiotics Fermentation Technology, a Novel Kefir Product, Ameliorates Cognitive Impairment in Streptozotocin-Induced Sporadic Alzheimer's Disease in Mice.Oxidative medicine and cellular longevity · 2021Article
- Self-Assembling Peptide Scaffold Carrying Neural-Cell Adhesion Molecule-Derived Mimetic-Peptide Transplantation Promotes Proliferation and Stimulates Neurite Extension by Modulating Tau Phosphorylation and Calpain/Glycogen Synthase Kinase 3 beta (GSK-3β) in Neurons.Annals of transplantation · 2020Article
- The functional microscopic neuroanatomy of the human subthalamic nucleus.Brain structure & function · 2019Article
- The role of neurofilament aggregation in neurodegeneration: lessons from rare inherited neurological disorders.Molecular neurodegeneration · 2019Review
- Peripheral Biomarkers for Early Detection of Alzheimer's and Parkinson's Diseases.Molecular neurobiology · 2019Review
- Involvement of calpain in the neuropathogenesis of Alzheimer's disease.Medicinal research reviews · 2019Review
- Nicotine is neuroprotective to neonatal neurons of sympathetic ganglion in rat.Autonomic neuroscience : basic & clinical · 2019Article
- Early Life Stress and Epigenetics in Late-onset Alzheimer's Dementia: A Systematic Review.Current genomics · 2018Review
- Regucalcin confers resistance to amyloid-β toxicity in neuronally differentiated PC12 cells.FEBS open bio · 2018Article
- Functional analyses of major cancer-related signaling pathways in Alzheimer's disease etiology.Biochimica et biophysica acta. Reviews on cancer · 2017Review
- Chronic traumatic encephalopathy-integration of canonical traumatic brain injury secondary injury mechanisms with tau pathology.Progress in neurobiology · 2017Review
4 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
15 authors at 3 institutions in 2 countries.
Funding
Abstract
Aberrant phosphorylation of the neuronal cytoskeleton is an early pathological event in Alzheimer's disease (AD), but the underlying mechanisms are unclear. Here, we demonstrate in the brains of AD patients that neurofilament hyperphosphorylation in neocortical pyramidal neurons is accompanied by activation of both Erk1,2 and calpain. Using immunochemistry, Western blot analysis, and kinase activity measurements, we show in primary hippocampal and cerebellar granule (CG) neurons that calcium influx activates calpain and Erk1,2 and increases neurofilament phosphorylation on carboxy terminal polypeptide sites known to be modulated by Erk1,2 and to be altered in AD. Blocking Erk1,2 activity either with antisense oligonucleotides to Erk1,2 mRNA sequences or by specifically inhibiting its upstream activating kinase MEK1,2 markedly reduced neurofilament phosphorylation. Calpeptin, a cell-permeable calpain inhibitor, blocked both Erk1,2 activation and neurofilament hyperphosphorylation at concentrations that inhibit calpain-mediated cleavage of brain spectrin. By contrast, inhibiting Erk1,2 with U-0126, a specific inhibitor of Mek1,2, had no appreciable effect on ionomycin-induced calpain activation. These findings demonstrate that, under conditions of calcium injury in neurons, calpains are upstream activators of Erk1,2 signaling and are likely to mediate in part the hyperphosphorylation of neurofilaments and tau seen at early stages of AD as well as the neuron survival-related functions of the MAP kinase 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.