Broad neutralization of calcium-permeable amyloid pore channels with a chimeric Alzheimer/Parkinson peptide targeting brain gangliosides.
Identifieur interne : 000339 ( Main/Exploration ); précédent : 000338; suivant : 000340Broad neutralization of calcium-permeable amyloid pore channels with a chimeric Alzheimer/Parkinson peptide targeting brain gangliosides.
Auteurs : Coralie Di Scala [France] ; Nouara Yahi [France] ; Alessandra Flores [France] ; Sonia Boutemeur [France] ; Nazim Kourdougli [France] ; Henri Chahinian [France] ; Jacques Fantini [France]Source :
- Biochimica et biophysica acta [ 0006-3002 ] ; 2016.
Abstract
Growing evidence supports a role for brain gangliosides in the pathogenesis of neurodegenerative diseases including Alzheimer's and Parkinson's. Recently we deciphered the ganglioside-recognition code controlling specific ganglioside binding to Alzheimer's β-amyloid (Aβ1-42) peptide and Parkinson's disease-associated protein α-synuclein. Cracking this code allowed us to engineer a short chimeric Aβ/α-synuclein peptide that recognizes all brain gangliosides. Here we show that ganglioside-deprived neural cells do no longer sustain the formation of zinc-sensitive amyloid pore channels induced by either Aβ1-42 or α-synuclein, as assessed by single-cell Ca(2+) fluorescence microscopy. Thus, amyloid channel formation, now considered a key step in neurodegeneration, is a ganglioside-dependent process. Nanomolar concentrations of chimeric peptide competitively inhibited amyloid pore formation induced by Aβ1-42 or α-synuclein in cultured neural cells. Moreover, this peptide abrogated the intracellular calcium increases induced by Parkinson's-associated mutant forms of α-synuclein (A30P, E46K and A53T). The chimeric peptide also prevented the deleterious effects of Aβ1-42 on synaptic vesicle trafficking and decreased the Aβ1-42-induced impairment of spontaneous activity in rat hippocampal slices. Taken together, these data show that the chimeric peptide has broad anti-amyloid pore activity, suggesting that a common therapeutic strategy based on the prevention of amyloid-ganglioside interactions is a reachable goal for both Alzheimer's and Parkinson's diseases.
DOI: 10.1016/j.bbadis.2015.11.012
PubMed: 26655601
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: 000192
- to stream PubMed, to step Curation: 000192
- to stream PubMed, to step Checkpoint: 000192
- to stream Ncbi, to step Merge: 001894
- to stream Ncbi, to step Curation: 001894
- to stream Ncbi, to step Checkpoint: 001894
- to stream Main, to step Merge: 000341
- to stream Main, to step Curation: 000339
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Broad neutralization of calcium-permeable amyloid pore channels with a chimeric Alzheimer/Parkinson peptide targeting brain gangliosides.</title><author><name sortKey="Di Scala, Coralie" sort="Di Scala, Coralie" uniqKey="Di Scala C" first="Coralie" last="Di Scala">Coralie Di Scala</name><affiliation wicri:level="4"><nlm:affiliation>Aix-Marseille Université, PPSN-EA4674, Faculté des Sciences, Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Aix-Marseille Université, PPSN-EA4674, Faculté des Sciences, Marseille</wicri:regionArea><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName><orgName type="university">Université d'Aix-Marseille</orgName></affiliation></author><author><name sortKey="Yahi, Nouara" sort="Yahi, Nouara" uniqKey="Yahi N" first="Nouara" last="Yahi">Nouara Yahi</name><affiliation wicri:level="4"><nlm:affiliation>Aix-Marseille Université, PPSN-EA4674, Faculté des Sciences, Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Aix-Marseille Université, PPSN-EA4674, Faculté des Sciences, Marseille</wicri:regionArea><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName><orgName type="university">Université d'Aix-Marseille</orgName></affiliation></author><author><name sortKey="Flores, Alessandra" sort="Flores, Alessandra" uniqKey="Flores A" first="Alessandra" last="Flores">Alessandra Flores</name><affiliation wicri:level="4"><nlm:affiliation>Aix-Marseille Université, PPSN-EA4674, Faculté des Sciences, Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Aix-Marseille Université, PPSN-EA4674, Faculté des Sciences, Marseille</wicri:regionArea><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName><orgName type="university">Université d'Aix-Marseille</orgName></affiliation></author><author><name sortKey="Boutemeur, Sonia" sort="Boutemeur, Sonia" uniqKey="Boutemeur S" first="Sonia" last="Boutemeur">Sonia Boutemeur</name><affiliation wicri:level="4"><nlm:affiliation>Aix-Marseille Université, PPSN-EA4674, Faculté des Sciences, Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Aix-Marseille Université, PPSN-EA4674, Faculté des Sciences, Marseille</wicri:regionArea><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName><orgName type="university">Université d'Aix-Marseille</orgName></affiliation></author><author><name sortKey="Kourdougli, Nazim" sort="Kourdougli, Nazim" uniqKey="Kourdougli N" first="Nazim" last="Kourdougli">Nazim Kourdougli</name><affiliation wicri:level="3"><nlm:affiliation>INSERM, INMED, Parc Scientifique de Luminy, 13009 Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM, INMED, Parc Scientifique de Luminy, 13009 Marseille</wicri:regionArea><placeName><region type="region" nuts="2">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Chahinian, Henri" sort="Chahinian, Henri" uniqKey="Chahinian H" first="Henri" last="Chahinian">Henri Chahinian</name><affiliation wicri:level="4"><nlm:affiliation>Aix-Marseille Université, PPSN-EA4674, Faculté des Sciences, Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Aix-Marseille Université, PPSN-EA4674, Faculté des Sciences, Marseille</wicri:regionArea><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName><orgName type="university">Université d'Aix-Marseille</orgName></affiliation></author><author><name sortKey="Fantini, Jacques" sort="Fantini, Jacques" uniqKey="Fantini J" first="Jacques" last="Fantini">Jacques Fantini</name><affiliation wicri:level="4"><nlm:affiliation>Aix-Marseille Université, PPSN-EA4674, Faculté des Sciences, Marseille, France. Electronic address: jacques.fantini@univ-amu.fr.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Aix-Marseille Université, PPSN-EA4674, Faculté des Sciences, Marseille</wicri:regionArea><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName><orgName type="university">Université d'Aix-Marseille</orgName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2016">2016</date><idno type="RBID">pubmed:26655601</idno><idno type="pmid">26655601</idno><idno type="doi">10.1016/j.bbadis.2015.11.012</idno><idno type="wicri:Area/PubMed/Corpus">000192</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000192</idno><idno type="wicri:Area/PubMed/Curation">000192</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000192</idno><idno type="wicri:Area/PubMed/Checkpoint">000192</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000192</idno><idno type="wicri:Area/Ncbi/Merge">001894</idno><idno type="wicri:Area/Ncbi/Curation">001894</idno><idno type="wicri:Area/Ncbi/Checkpoint">001894</idno><idno type="wicri:doubleKey">0006-3002:2016:Di Scala C:broad:neutralization:of</idno><idno type="wicri:Area/Main/Merge">000341</idno><idno type="wicri:Area/Main/Curation">000339</idno><idno type="wicri:Area/Main/Exploration">000339</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Broad neutralization of calcium-permeable amyloid pore channels with a chimeric Alzheimer/Parkinson peptide targeting brain gangliosides.</title><author><name sortKey="Di Scala, Coralie" sort="Di Scala, Coralie" uniqKey="Di Scala C" first="Coralie" last="Di Scala">Coralie Di Scala</name><affiliation wicri:level="4"><nlm:affiliation>Aix-Marseille Université, PPSN-EA4674, Faculté des Sciences, Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Aix-Marseille Université, PPSN-EA4674, Faculté des Sciences, Marseille</wicri:regionArea><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName><orgName type="university">Université d'Aix-Marseille</orgName></affiliation></author><author><name sortKey="Yahi, Nouara" sort="Yahi, Nouara" uniqKey="Yahi N" first="Nouara" last="Yahi">Nouara Yahi</name><affiliation wicri:level="4"><nlm:affiliation>Aix-Marseille Université, PPSN-EA4674, Faculté des Sciences, Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Aix-Marseille Université, PPSN-EA4674, Faculté des Sciences, Marseille</wicri:regionArea><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName><orgName type="university">Université d'Aix-Marseille</orgName></affiliation></author><author><name sortKey="Flores, Alessandra" sort="Flores, Alessandra" uniqKey="Flores A" first="Alessandra" last="Flores">Alessandra Flores</name><affiliation wicri:level="4"><nlm:affiliation>Aix-Marseille Université, PPSN-EA4674, Faculté des Sciences, Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Aix-Marseille Université, PPSN-EA4674, Faculté des Sciences, Marseille</wicri:regionArea><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName><orgName type="university">Université d'Aix-Marseille</orgName></affiliation></author><author><name sortKey="Boutemeur, Sonia" sort="Boutemeur, Sonia" uniqKey="Boutemeur S" first="Sonia" last="Boutemeur">Sonia Boutemeur</name><affiliation wicri:level="4"><nlm:affiliation>Aix-Marseille Université, PPSN-EA4674, Faculté des Sciences, Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Aix-Marseille Université, PPSN-EA4674, Faculté des Sciences, Marseille</wicri:regionArea><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName><orgName type="university">Université d'Aix-Marseille</orgName></affiliation></author><author><name sortKey="Kourdougli, Nazim" sort="Kourdougli, Nazim" uniqKey="Kourdougli N" first="Nazim" last="Kourdougli">Nazim Kourdougli</name><affiliation wicri:level="3"><nlm:affiliation>INSERM, INMED, Parc Scientifique de Luminy, 13009 Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM, INMED, Parc Scientifique de Luminy, 13009 Marseille</wicri:regionArea><placeName><region type="region" nuts="2">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Chahinian, Henri" sort="Chahinian, Henri" uniqKey="Chahinian H" first="Henri" last="Chahinian">Henri Chahinian</name><affiliation wicri:level="4"><nlm:affiliation>Aix-Marseille Université, PPSN-EA4674, Faculté des Sciences, Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Aix-Marseille Université, PPSN-EA4674, Faculté des Sciences, Marseille</wicri:regionArea><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName><orgName type="university">Université d'Aix-Marseille</orgName></affiliation></author><author><name sortKey="Fantini, Jacques" sort="Fantini, Jacques" uniqKey="Fantini J" first="Jacques" last="Fantini">Jacques Fantini</name><affiliation wicri:level="4"><nlm:affiliation>Aix-Marseille Université, PPSN-EA4674, Faculté des Sciences, Marseille, France. Electronic address: jacques.fantini@univ-amu.fr.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Aix-Marseille Université, PPSN-EA4674, Faculté des Sciences, Marseille</wicri:regionArea><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName><orgName type="university">Université d'Aix-Marseille</orgName></affiliation></author></analytic><series><title level="j">Biochimica et biophysica acta</title><idno type="ISSN">0006-3002</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Growing evidence supports a role for brain gangliosides in the pathogenesis of neurodegenerative diseases including Alzheimer's and Parkinson's. Recently we deciphered the ganglioside-recognition code controlling specific ganglioside binding to Alzheimer's β-amyloid (Aβ1-42) peptide and Parkinson's disease-associated protein α-synuclein. Cracking this code allowed us to engineer a short chimeric Aβ/α-synuclein peptide that recognizes all brain gangliosides. Here we show that ganglioside-deprived neural cells do no longer sustain the formation of zinc-sensitive amyloid pore channels induced by either Aβ1-42 or α-synuclein, as assessed by single-cell Ca(2+) fluorescence microscopy. Thus, amyloid channel formation, now considered a key step in neurodegeneration, is a ganglioside-dependent process. Nanomolar concentrations of chimeric peptide competitively inhibited amyloid pore formation induced by Aβ1-42 or α-synuclein in cultured neural cells. Moreover, this peptide abrogated the intracellular calcium increases induced by Parkinson's-associated mutant forms of α-synuclein (A30P, E46K and A53T). The chimeric peptide also prevented the deleterious effects of Aβ1-42 on synaptic vesicle trafficking and decreased the Aβ1-42-induced impairment of spontaneous activity in rat hippocampal slices. Taken together, these data show that the chimeric peptide has broad anti-amyloid pore activity, suggesting that a common therapeutic strategy based on the prevention of amyloid-ganglioside interactions is a reachable goal for both Alzheimer's and Parkinson's diseases.</div></front></TEI><affiliations><list><country><li>France</li></country><region><li>Provence-Alpes-Côte d'Azur</li></region><settlement><li>Marseille</li></settlement><orgName><li>Université d'Aix-Marseille</li></orgName></list><tree><country name="France"><region name="Provence-Alpes-Côte d'Azur"><name sortKey="Di Scala, Coralie" sort="Di Scala, Coralie" uniqKey="Di Scala C" first="Coralie" last="Di Scala">Coralie Di Scala</name></region><name sortKey="Boutemeur, Sonia" sort="Boutemeur, Sonia" uniqKey="Boutemeur S" first="Sonia" last="Boutemeur">Sonia Boutemeur</name><name sortKey="Chahinian, Henri" sort="Chahinian, Henri" uniqKey="Chahinian H" first="Henri" last="Chahinian">Henri Chahinian</name><name sortKey="Fantini, Jacques" sort="Fantini, Jacques" uniqKey="Fantini J" first="Jacques" last="Fantini">Jacques Fantini</name><name sortKey="Flores, Alessandra" sort="Flores, Alessandra" uniqKey="Flores A" first="Alessandra" last="Flores">Alessandra Flores</name><name sortKey="Kourdougli, Nazim" sort="Kourdougli, Nazim" uniqKey="Kourdougli N" first="Nazim" last="Kourdougli">Nazim Kourdougli</name><name sortKey="Yahi, Nouara" sort="Yahi, Nouara" uniqKey="Yahi N" first="Nouara" last="Yahi">Nouara Yahi</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/ParkinsonFranceV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000339 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000339 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Sante
|area= ParkinsonFranceV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= pubmed:26655601
|texte= Broad neutralization of calcium-permeable amyloid pore channels with a chimeric Alzheimer/Parkinson peptide targeting brain gangliosides.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:26655601" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a ParkinsonFranceV1
| This area was generated with Dilib version V0.6.29. |  |