ArticleNeuropharmacology2016
A calpain-2 selective inhibitor enhances learning & memory by prolonging ERK activation.
Article in Neuropharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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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.
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Who cites it
19 citing papers in PubMed, 36 citations in OpenAlex.
- Calpain-1 Potentiates Periodontal Regeneration via PHLPP1-ERK-Driven Osteogenesis in Periodontal Ligament Stem Cells.International dental journal · 2026Article
- Ubiquitous calpastatin overexpression in brain-injured mice attenuates motor and cognitive behavioral deficits without overt neuroprotection.Molecular and cellular neurosciences · 2025Article
- Article
- Identification and neuroprotective properties of NA-184, a calpain-2 inhibitor.Pharmacology research & perspectives · 2024Article
- Revisiting the calpain hypothesis of learning and memory 40 years later.Frontiers in molecular neuroscience · 2024Review
- The Alpha Keto Amide Moiety as a Privileged Motif in Medicinal Chemistry: Current Insights and Emerging Opportunities.Journal of medicinal chemistry · 2021Review
- Changes in neurodegeneration-related miRNAs in brains from CAPN1BBA advances · 2021Article
- Involvement of calpain in the neuropathogenesis of Alzheimer's disease.Medicinal research reviews · 2019Review
- Proteolytic Degradation of Hippocampal STEPMolecular neurobiology · 2019Article
- Calpain-1 and Calpain-2 in the Brain: Dr. Jekill and Mr Hyde?Current neuropharmacology · 2019Review
- EZH2 Methyltransferase Activity Controls Pten Expression and mTOR Signaling during Fear Memory Reconsolidation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- M-Calpain Activation Facilitates Seizure Induced KCC2 Down Regulation.Frontiers in molecular neuroscience · 2018Article
- Protection against TBI-Induced Neuronal Death with Post-Treatment with a Selective Calpain-2 Inhibitor in Mice.Journal of neurotrauma · 2018Article
- Calpain-2 as a therapeutic target for acute neuronal injury.Expert opinion on therapeutic targets · 2018Review
- The tyrosine phosphatase PTPN13/FAP-1 links calpain-2, TBI and tau tyrosine phosphorylation.Scientific reports · 2017Article
- Calpain-GRIP Signaling in Nucleus Accumbens Core Mediates the Reconsolidation of Drug Reward Memory.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- Article
- Differential role of calpain-dependent protein cleavage in intermediate and long-term operant memory in Aplysia.Neurobiology of learning and memory · 2017Article
- Deleting both PHLPP1 and CANP1 rescues impairments in long-term potentiation and learning in both single knockout mice.Learning & memory (Cold Spring Harbor, N.Y.) · 2016Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
While calpain-1 activation is required for LTP induction by theta burst stimulation (TBS), calpain-2 activation limits its magnitude during the consolidation period. A selective calpain-2 inhibitor applied either before or shortly after TBS enhanced the degree of potentiation. In the present study, we tested whether the selective calpain-2 inhibitor, Z-Leu-Abu-CONH-CH2-C6H3 (3, 5-(OMe)2 (C2I), could enhance learning and memory in wild-type (WT) and calpain-1 knock-out (C1KO) mice. We first showed that C2I could reestablish TBS-LTP in hippocampal slices from C1KO mice, and this effect was blocked by PD98059, an inhibitor of ERK. TBS resulted in PTEN degradation in hippocampal slices from both WT and C1KO mice, and C2I treatment blocked this effect in both mouse genotypes. Systemic injection of C2I 30 min before training in the fear-conditioning paradigm resulted in a biphasic dose-response curve, with low doses enhancing and high doses inhibiting freezing behavior. The difference between the doses needed to enhance and inhibit learning matches the difference in concentrations producing inhibition of calpain-2 and calpain-1. A low dose of C2I also restored normal learning in a novel object recognition task in C1KO mice. Levels of SCOP, a ERK phosphatase known to be cleaved by calpain-1, were decreased in dorsal hippocampus early but not late following training in WT mice; C2I treatment did not affect the early decrease in SCOP levels but prevented its recovery at the later time-point and prolonged ERK activation. The results indicate that calpain-2 activation limits the extent of learning, an effect possibly due to temporal limitation of ERK activation, as a result of SCOP synthesis induced by calpain-2-mediated PTEN degradation.
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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.