The IκB kinase inhibitor sulfasalazine impairs long-term memory in the crab Chasmagnathus

Merlo, Emiliano; Freudenthal, Ramiro; Romano, Arturo

doi:10.1016/s0306-4522(02)00049-0

Cited by 89 publications

(78 citation statements)

References 44 publications

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“…In this model, a high correlation between memory formation and NF-B activation was demonstrated (Freudenthal et al 1998;Freudenthal and Romano 2000). In addition, the inhibition of this TF by a specific IKK inhibitor, sulfasalazine, induced amnesia during the two periods in which NF-B was active (Merlo et al 2002). Moreover, activated NF-B was found in synaptic terminals after LTM induction, giving physiological support for the synapse-to-nucleus signaling role of NF-B (Freudenthal and Romano 2000).…”

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confidence: 62%

Activation of the transcription factor NF-κB by retrieval is required for long-term memory reconsolidation

Merlo¹,

Freudenthal²,

Maldonado³

et al. 2005

Learn. Mem.

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Several studies support that stored memories undergo a new period of consolidation after retrieval. It is not known whether this process, termed reconsolidation, requires the same transcriptional mechanisms involved in consolidation. Increasing evidence supports the participation of the transcription factor NF-B in memory. This was initially demonstrated in the crab Chasmagnathus model of associative contextual memory, in which re-exposure to the training context induces a well characterized reconsolidation process. Here we studied the role of NF-B in reconsolidation. NF-B was specifically activated in trained animals re-exposed to the training context but not to a different context. NF-B was not activated when animals were re-exposed to the context after a weak training protocol insufficient to induce long-term memory. A specific inhibitor of the NF-B pathway, sulfasalazine, impaired reconsolidation when administered 20 min before re-exposure to the training context but was not effective when a different context was used. These findings indicate for the first time that NF-B is activated specifically by retrieval and that this activation is required for memory reconsolidation, supporting the view that this molecular mechanism is required in both consolidation and reconsolidation.

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confidence: 62%

Activation of the transcription factor NF-κB by retrieval is required for long-term memory reconsolidation

Merlo¹,

Freudenthal²,

Maldonado³

et al. 2005

Learn. Mem.

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“…The two NF-B-inhibiting marine natural products macrolide bryostatin 1 isolated from a bryozoan [56] and salinosporamide A isolated from a bacterium [24] are currently in clinical trials [58]. Several ecological reasons why marine natural products may inhibit NF-B have been established [20,21,[59][60][61][62][63][64][65][66][67][68][69].…”

Section: Discussionmentioning

confidence: 99%

The inhibition of TNF-α-induced NF-κB activation by marine natural products

Folmer

Jaspars

Solano

et al. 2009

Biochemical Pharmacology

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, et al.. The inhibition of TNF-α induced NF-κB activation by marine natural products. Biochemical Pharmacology, Elsevier, 2009, 78 (6) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 AbstractThe deregulated activation of NF-B is associated with cancer development and inflammatory diseases. With the aim to find new NF-B inhibitors, we purified and characterized compounds from extracts of the Fijian sponge Rhabdastrella globostellata, the crinoid Comanthus parvicirrus, the soft corals Sarcophyton sp. nov. and Sinularia sp., and the gorgonian Subergorgia sp. after an initial screening of 266 extracts from different marine origins.Results obtained show that selected purified compounds had a cytotoxic effect on the human leukaemia cell line K562, inhibited both TNF--induced NF-B-DNA binding as well as TNF- induced IB degradation and nuclear translocation of p50/p65. Furthermore, we observed inhibition of NF-B activation induced by an overexpression of TNFR1, TRAF2, TRADD, or IKK Interestingly, natural products inhibited IKK kinase as well as the 26S proteasome proteolytic activity.

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“…Interestingly, the human PKM mRNA promoter has an additional partial CRE insert that might enhance the binding of CREB and the activity-dependent transcription of PKM mRNA. The PKM mRNA promoter region also contains putative binding sites for other transcription factors implicated in memory, including Nf-B and C/EBP (37)(38)(39).…”

Section: Pkm Is Expressed Exclusively In Brain-vertebrates Ex-mentioning

confidence: 99%

Protein Kinase Mζ Synthesis from a Brain mRNA Encoding an Independent Protein Kinase Cζ Catalytic Domain

Hernández

Blace

Crary

et al. 2003

Journal of Biological Chemistry

254

295

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Protein kinase M (PKM) is a newly described form of PKC that is necessary and sufficient for the maintenance of hippocampal long term potentiation (LTP) and the persistence of memory in Drosophila. PKM is the independent catalytic domain of the atypical PKC isoform and produces long term effects at synapses because it is persistently active, lacking autoinhibition from the regulatory domain of PKC. PKM has been thought of as a proteolytic fragment of PKC. Here we report that brain PKM is a new PKC isoform, synthesized from a PKM mRNA encoding a PKC catalytic domain without a regulatory domain. Multiple -specific antisera show that PKM is expressed in rat forebrain as the major form of in the near absence of full-length PKC. A PKC knockout mouse, in which the regulatory domain was disrupted and catalytic domain spared, still expresses brain PKM, indicating that this form of PKM is not a PKC proteolytic fragment. Furthermore, the distribution of brain PKM does not correlate with PKC mRNA but instead with an alternate RNA transcript thought incapable of producing protein. In vitro translation of this RNA, however, generates PKM of the same molecular weight as that in brain. Metabolic labeling of hippocampal slices shows increased de novo synthesis of PKM in LTP. Because PKM is a kinase synthesized in an autonomously active form and is necessary and sufficient for maintaining LTP, it serves as an example of a link coupling gene expression directly to synaptic plasticity. LTP1 is a persistent enhancement of synaptic transmission widely studied as a physiological model of memory (1). LTP can be divided into two phases: induction, which triggers the potentiation, and maintenance, which sustains it over time. Many molecules have been implicated in LTP induction, which is initiated by the activation of N-methyl-D-aspartate (NMDA) receptors and involves several protein kinases (2). In contrast, very little is known about the molecular mechanism of maintenance. Recently, however, a specific, autonomously active form of the atypical PKC isozyme (3, 4), PKM, has been found both necessary and sufficient for maintaining LTP (5-7). Overexpression of PKM also prolongs memory in Drosophila melanogaster, suggesting it is part of an evolutionarily conserved molecular mechanism for memory storage (8).The unique role of PKM in LTP maintenance is due, in part, to its unusual structural and enzymatic properties as an autonomously active kinase. PKM consists of the independent catalytic domain of a PKC isoform (5). PKC isoforms are divided into three classes: conventional, novel, and atypical (reviewed in Refs. 9 -11). Each isoform is a single polypeptide consisting of an N-terminal regulatory domain and a C-terminal catalytic domain linked by a hinge (Fig. 1A, left). The regulatory domain contains binding sites for second messengers and an autoinhibitory pseudosubstrate sequence, which interacts with and blocks the active site of the catalytic domain. Second messengers stimulate PKC by binding to the regulatory domain, translocating th...

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The IκB kinase inhibitor sulfasalazine impairs long-term memory in the crab Chasmagnathus

Cited by 89 publications

References 44 publications

Activation of the transcription factor NF-κB by retrieval is required for long-term memory reconsolidation

Activation of the transcription factor NF-κB by retrieval is required for long-term memory reconsolidation

The inhibition of TNF-α-induced NF-κB activation by marine natural products

Protein Kinase Mζ Synthesis from a Brain mRNA Encoding an Independent Protein Kinase Cζ Catalytic Domain

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