Synaptic pathophysiology and treatment of Lambert-Eaton myasthenic syndrome
Identifieur interne : 001067 ( Main/Exploration ); précédent : 001066; suivant : 001068Synaptic pathophysiology and treatment of Lambert-Eaton myasthenic syndrome
Auteurs : Tyler B. Tarr [États-Unis] ; Peter Wipf [États-Unis] ; Stephen D. Meriney [États-Unis]Source :
- Molecular neurobiology [ 0893-7648 ] ; 2014.
Descripteurs français
- KwdFr :
- Animaux, Humains, Jonction neuromusculaire (), Jonction neuromusculaire (physiopathologie), Neuroprotecteurs (pharmacologie), Neuroprotecteurs (usage thérapeutique), Synapses (), Synapses (anatomopathologie), Syndrome myasthénique de Lambert-Eaton (), Syndrome myasthénique de Lambert-Eaton (physiopathologie), Syndrome myasthénique de Lambert-Eaton (traitement médicamenteux).
- MESH :
- anatomopathologie : Synapses.
- pharmacologie : Neuroprotecteurs.
- physiopathologie : Jonction neuromusculaire, Syndrome myasthénique de Lambert-Eaton.
- traitement médicamenteux : Syndrome myasthénique de Lambert-Eaton.
- usage thérapeutique : Neuroprotecteurs.
- Animaux, Humains, Jonction neuromusculaire, Synapses, Syndrome myasthénique de Lambert-Eaton.
English descriptors
- KwdEn :
- Animals, Humans, Lambert-Eaton Myasthenic Syndrome (drug therapy), Lambert-Eaton Myasthenic Syndrome (physiopathology), Lambert-Eaton Myasthenic Syndrome (therapy), Neuromuscular Junction (drug effects), Neuromuscular Junction (physiopathology), Neuroprotective Agents (pharmacology), Neuroprotective Agents (therapeutic use), Synapses (drug effects), Synapses (pathology).
- MESH :
- chemical , pharmacology : Neuroprotective Agents.
- drug effects : Neuromuscular Junction, Synapses.
- drug therapy : Lambert-Eaton Myasthenic Syndrome.
- pathology : Synapses.
- physiopathology : Lambert-Eaton Myasthenic Syndrome, Neuromuscular Junction.
- chemical , therapeutic use : Neuroprotective Agents.
- therapy : Lambert-Eaton Myasthenic Syndrome.
- Animals, Humans.
Abstract
Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disease that disrupts the normally reliable neurotransmission at the neuromuscular junction (NMJ). This disruption is thought to result from an autoantibody-mediated removal of a subset of the P/Q-type Ca2+ channels involved with neurotransmitter release. With less neurotransmitter release at the NMJ, LEMS patients experience debilitating muscle weakness. The underlying cause of LEMS in slightly more than half of all patients is small-cell lung cancer, and cancer therapy is the priority for these patients. In the remaining cases, the cause of LEMS is unknown and these patients often rely on symptomatic treatment options as there is no cure. However, current symptomatic treatment options, such as 3,4-diaminopyridine (3,4-DAP), can have significant dose-limiting side effects; thus, additional treatment approaches would benefit LEMS patients. Recent studies introduced a novel Ca2+ channel agonist (GV-58) as a potential therapeutic alternative for LEMS. Additionally, this work has shown that GV-58 and 3,4-DAP interact in a supra-additive manner to completely restore the magnitude of neurotransmitter release at the NMJs of a LEMS mouse model. In this review, we discuss synaptic mechanisms for reliability at the NMJ and how these mechanisms are disrupted in LEMS. We then discuss the current treatment options for LEMS patients, while also considering recent work demonstrating the therapeutic potential of GV-58 alone and in combination with 3,4-DAP.
Url:
DOI: 10.1007/s12035-014-8887-2
PubMed: 25195700
PubMed Central: 4362862
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: 001710
- to stream Pmc, to step Curation: 001685
- to stream Pmc, to step Checkpoint: 000471
- to stream PubMed, to step Corpus: 000160
- to stream PubMed, to step Curation: 000160
- to stream PubMed, to step Checkpoint: 000160
- to stream Ncbi, to step Merge: 003411
- to stream Ncbi, to step Curation: 003411
- to stream Ncbi, to step Checkpoint: 003411
- to stream Main, to step Merge: 001090
- to stream Main, to step Curation: 001067
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Synaptic pathophysiology and treatment of Lambert-Eaton myasthenic syndrome</title><author><name sortKey="Tarr, Tyler B" sort="Tarr, Tyler B" uniqKey="Tarr T" first="Tyler B." last="Tarr">Tyler B. Tarr</name><affiliation wicri:level="4"><nlm:aff id="A1">Department of Neuroscience, Center for Neuroscience at the University of Pittsburgh, and Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, PA 15260, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neuroscience, Center for Neuroscience at the University of Pittsburgh, and Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, PA 15260</wicri:regionArea><placeName><region type="state">Pennsylvanie</region><settlement type="city">Pittsburgh</settlement></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation></author><author><name sortKey="Wipf, Peter" sort="Wipf, Peter" uniqKey="Wipf P" first="Peter" last="Wipf">Peter Wipf</name><affiliation wicri:level="4"><nlm:aff id="A2">Department of Chemistry and Center for Chemical Methodologies and Library Development, University of Pittsburgh, Pittsburgh, PA 15260, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Chemistry and Center for Chemical Methodologies and Library Development, University of Pittsburgh, Pittsburgh, PA 15260</wicri:regionArea><placeName><region type="state">Pennsylvanie</region><settlement type="city">Pittsburgh</settlement></placeName><orgName type="university">Université de Pittsburgh</orgName><placeName><settlement type="city">Pittsburgh</settlement><region type="state">Pennsylvanie</region></placeName><orgName type="university" n="3">Université de Pittsburgh</orgName></affiliation></author><author><name sortKey="Meriney, Stephen D" sort="Meriney, Stephen D" uniqKey="Meriney S" first="Stephen D." last="Meriney">Stephen D. Meriney</name><affiliation wicri:level="4"><nlm:aff id="A1">Department of Neuroscience, Center for Neuroscience at the University of Pittsburgh, and Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, PA 15260, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neuroscience, Center for Neuroscience at the University of Pittsburgh, and Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, PA 15260</wicri:regionArea><placeName><region type="state">Pennsylvanie</region><settlement type="city">Pittsburgh</settlement></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">25195700</idno><idno type="pmc">4362862</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4362862</idno><idno type="RBID">PMC:4362862</idno><idno type="doi">10.1007/s12035-014-8887-2</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">001710</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001710</idno><idno type="wicri:Area/Pmc/Curation">001685</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">001685</idno><idno type="wicri:Area/Pmc/Checkpoint">000471</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000471</idno><idno type="wicri:source">PubMed</idno><idno type="wicri:Area/PubMed/Corpus">000160</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000160</idno><idno type="wicri:Area/PubMed/Curation">000160</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000160</idno><idno type="wicri:Area/PubMed/Checkpoint">000160</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000160</idno><idno type="wicri:Area/Ncbi/Merge">003411</idno><idno type="wicri:Area/Ncbi/Curation">003411</idno><idno type="wicri:Area/Ncbi/Checkpoint">003411</idno><idno type="wicri:doubleKey">0893-7648:2014:Tarr T:synaptic:pathophysiology:and</idno><idno type="wicri:Area/Main/Merge">001090</idno><idno type="wicri:Area/Main/Curation">001067</idno><idno type="wicri:Area/Main/Exploration">001067</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Synaptic pathophysiology and treatment of Lambert-Eaton myasthenic syndrome</title><author><name sortKey="Tarr, Tyler B" sort="Tarr, Tyler B" uniqKey="Tarr T" first="Tyler B." last="Tarr">Tyler B. Tarr</name><affiliation wicri:level="4"><nlm:aff id="A1">Department of Neuroscience, Center for Neuroscience at the University of Pittsburgh, and Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, PA 15260, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neuroscience, Center for Neuroscience at the University of Pittsburgh, and Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, PA 15260</wicri:regionArea><placeName><region type="state">Pennsylvanie</region><settlement type="city">Pittsburgh</settlement></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation></author><author><name sortKey="Wipf, Peter" sort="Wipf, Peter" uniqKey="Wipf P" first="Peter" last="Wipf">Peter Wipf</name><affiliation wicri:level="4"><nlm:aff id="A2">Department of Chemistry and Center for Chemical Methodologies and Library Development, University of Pittsburgh, Pittsburgh, PA 15260, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Chemistry and Center for Chemical Methodologies and Library Development, University of Pittsburgh, Pittsburgh, PA 15260</wicri:regionArea><placeName><region type="state">Pennsylvanie</region><settlement type="city">Pittsburgh</settlement></placeName><orgName type="university">Université de Pittsburgh</orgName><placeName><settlement type="city">Pittsburgh</settlement><region type="state">Pennsylvanie</region></placeName><orgName type="university" n="3">Université de Pittsburgh</orgName></affiliation></author><author><name sortKey="Meriney, Stephen D" sort="Meriney, Stephen D" uniqKey="Meriney S" first="Stephen D." last="Meriney">Stephen D. Meriney</name><affiliation wicri:level="4"><nlm:aff id="A1">Department of Neuroscience, Center for Neuroscience at the University of Pittsburgh, and Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, PA 15260, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neuroscience, Center for Neuroscience at the University of Pittsburgh, and Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, PA 15260</wicri:regionArea><placeName><region type="state">Pennsylvanie</region><settlement type="city">Pittsburgh</settlement></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation></author></analytic><series><title level="j">Molecular neurobiology</title><idno type="ISSN">0893-7648</idno><idno type="eISSN">1559-1182</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Humans</term><term>Lambert-Eaton Myasthenic Syndrome (drug therapy)</term><term>Lambert-Eaton Myasthenic Syndrome (physiopathology)</term><term>Lambert-Eaton Myasthenic Syndrome (therapy)</term><term>Neuromuscular Junction (drug effects)</term><term>Neuromuscular Junction (physiopathology)</term><term>Neuroprotective Agents (pharmacology)</term><term>Neuroprotective Agents (therapeutic use)</term><term>Synapses (drug effects)</term><term>Synapses (pathology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Humains</term><term>Jonction neuromusculaire ()</term><term>Jonction neuromusculaire (physiopathologie)</term><term>Neuroprotecteurs (pharmacologie)</term><term>Neuroprotecteurs (usage thérapeutique)</term><term>Synapses ()</term><term>Synapses (anatomopathologie)</term><term>Syndrome myasthénique de Lambert-Eaton ()</term><term>Syndrome myasthénique de Lambert-Eaton (physiopathologie)</term><term>Syndrome myasthénique de Lambert-Eaton (traitement médicamenteux)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Neuroprotective Agents</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Synapses</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Neuromuscular Junction</term><term>Synapses</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Lambert-Eaton Myasthenic Syndrome</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Synapses</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Neuroprotecteurs</term></keywords><keywords scheme="MESH" qualifier="physiopathologie" xml:lang="fr"><term>Jonction neuromusculaire</term><term>Syndrome myasthénique de Lambert-Eaton</term></keywords><keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><term>Lambert-Eaton Myasthenic Syndrome</term><term>Neuromuscular Junction</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Neuroprotective Agents</term></keywords><keywords scheme="MESH" qualifier="therapy" xml:lang="en"><term>Lambert-Eaton Myasthenic Syndrome</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Syndrome myasthénique de Lambert-Eaton</term></keywords><keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Neuroprotecteurs</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Humans</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Humains</term><term>Jonction neuromusculaire</term><term>Synapses</term><term>Syndrome myasthénique de Lambert-Eaton</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disease that disrupts the normally reliable neurotransmission at the neuromuscular junction (NMJ). This disruption is thought to result from an autoantibody-mediated removal of a subset of the P/Q-type Ca<sup>2+</sup> channels involved with neurotransmitter release. With less neurotransmitter release at the NMJ, LEMS patients experience debilitating muscle weakness. The underlying cause of LEMS in slightly more than half of all patients is small-cell lung cancer, and cancer therapy is the priority for these patients. In the remaining cases, the cause of LEMS is unknown and these patients often rely on symptomatic treatment options as there is no cure. However, current symptomatic treatment options, such as 3,4-diaminopyridine (3,4-DAP), can have significant dose-limiting side effects; thus, additional treatment approaches would benefit LEMS patients. Recent studies introduced a novel Ca<sup>2+</sup> channel agonist (GV-58) as a potential therapeutic alternative for LEMS. Additionally, this work has shown that GV-58 and 3,4-DAP interact in a supra-additive manner to completely restore the magnitude of neurotransmitter release at the NMJs of a LEMS mouse model. In this review, we discuss synaptic mechanisms for reliability at the NMJ and how these mechanisms are disrupted in LEMS. We then discuss the current treatment options for LEMS patients, while also considering recent work demonstrating the therapeutic potential of GV-58 alone and in combination with 3,4-DAP.</p></div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Pennsylvanie</li></region><settlement><li>Pittsburgh</li></settlement><orgName><li>Université de Pittsburgh</li></orgName></list><tree><country name="États-Unis"><region name="Pennsylvanie"><name sortKey="Tarr, Tyler B" sort="Tarr, Tyler B" uniqKey="Tarr T" first="Tyler B." last="Tarr">Tyler B. Tarr</name></region><name sortKey="Meriney, Stephen D" sort="Meriney, Stephen D" uniqKey="Meriney S" first="Stephen D." last="Meriney">Stephen D. Meriney</name><name sortKey="Wipf, Peter" sort="Wipf, Peter" uniqKey="Wipf P" first="Peter" last="Wipf">Peter Wipf</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Amérique/explor/PittsburghV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001067 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 001067 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Amérique
|area= PittsburghV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= PMC:4362862
|texte= Synaptic pathophysiology and treatment of Lambert-Eaton myasthenic syndrome
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:25195700" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a PittsburghV1
| This area was generated with Dilib version V0.6.38. |  |