Glucocerebrosidase gene therapy prevents α-synucleinopathy of midbrain dopamine neurons.
Identifieur interne : 000709 ( Main/Exploration ); précédent : 000708; suivant : 000710Glucocerebrosidase gene therapy prevents α-synucleinopathy of midbrain dopamine neurons.
Auteurs : Emily M. Rocha [États-Unis] ; Gaynor A. Smith [États-Unis] ; Eric Park [États-Unis] ; Hongmei Cao [États-Unis] ; Eilish Brown [États-Unis] ; Melissa A. Hayes [États-Unis] ; Jonathan Beagan [États-Unis] ; Jesse R. Mclean [États-Unis] ; Sarah C. Izen [États-Unis] ; Eduardo Perez-Torres [États-Unis] ; Penelope J. Hallett [États-Unis] ; Ole Isacson [États-Unis]Source :
- Neurobiology of disease [ 1095-953X ] ; 2015.
English descriptors
- KwdEn :
- Animals, Dependovirus (genetics), Disease Models, Animal, Dopamine (metabolism), Dopaminergic Neurons (enzymology), Dopaminergic Neurons (pathology), Female, Genetic Therapy (methods), Genetic Vectors, Glucosylceramidase (genetics), Glucosylceramidase (metabolism), Humans, Male, Mesencephalon (enzymology), Mesencephalon (pathology), Mice, Transgenic, Neurodegenerative Diseases (enzymology), Neurodegenerative Diseases (pathology), Neurodegenerative Diseases (therapy), Rats, Sprague-Dawley, alpha-Synuclein (genetics), alpha-Synuclein (metabolism).
- MESH :
- chemical , genetics : Glucosylceramidase, alpha-Synuclein.
- chemical , metabolism : Dopamine, Glucosylceramidase, alpha-Synuclein.
- enzymology : Dopaminergic Neurons, Mesencephalon, Neurodegenerative Diseases.
- genetics : Dependovirus.
- methods : Genetic Therapy.
- pathology : Dopaminergic Neurons, Mesencephalon, Neurodegenerative Diseases.
- therapy : Neurodegenerative Diseases.
- Animals, Disease Models, Animal, Female, Genetic Vectors, Humans, Male, Mice, Transgenic, Rats, Sprague-Dawley.
Abstract
Diminished lysosomal function can lead to abnormal cellular accumulation of specific proteins, including α-synuclein, contributing to disease pathogenesis of vulnerable neurons in Parkinson's disease (PD) and related α-synucleinopathies. GBA1 encodes for the lysosomal hydrolase glucocerebrosidase (GCase), and mutations in GBA1 are a prominent genetic risk factor for PD. Previous studies showed that in sporadic PD, and in normal aging, GCase brain activity is reduced and levels of corresponding glycolipid substrates are increased. The present study tested whether increasing GCase through AAV-GBA1 intra-cerebral gene delivery in two PD rodent models would reduce the accumulation of α-synuclein and protect midbrain dopamine neurons from α-synuclein-mediated neuronal damage. In the first model, transgenic mice overexpressing wildtype α-synuclein throughout the brain (ASO mice) were used, and in the second model, a rat model of selective dopamine neuron degeneration was induced by AAV-A53T mutant α-synuclein. In ASO mice, intra-cerebral AAV-GBA1 injections into several brain regions increased GCase activity and reduced the accumulation of α-synuclein in the substantia nigra and striatum. In rats, co-injection of AAV-GBA1 with AAV-A53T α-synuclein into the substantia nigra prevented α-synuclein-mediated degeneration of nigrostriatal dopamine neurons by 6 months. These neuroprotective effects were associated with altered protein expression of markers of autophagy. These experiments demonstrate, for the first time, the neuroprotective effects of increasing GCase against dopaminergic neuron degeneration, and support the development of therapeutics targeting GCase or other lysosomal genes to improve neuronal handling of α-synuclein.
DOI: 10.1016/j.nbd.2015.09.009
PubMed: 26392287
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: 000404
- to stream PubMed, to step Curation: 000404
- to stream PubMed, to step Checkpoint: 000404
- to stream Ncbi, to step Merge: 001D21
- to stream Ncbi, to step Curation: 001D21
- to stream Ncbi, to step Checkpoint: 001D21
- to stream Main, to step Merge: 000710
- to stream Main, to step Curation: 000709
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Glucocerebrosidase gene therapy prevents α-synucleinopathy of midbrain dopamine neurons.</title><author><name sortKey="Rocha, Emily M" sort="Rocha, Emily M" uniqKey="Rocha E" first="Emily M" last="Rocha">Emily M. Rocha</name><affiliation wicri:level="2"><nlm:affiliation>Neuroregeneration Research Institute, Harvard Medical School/McLean Hospital, Belmont, MA 02478, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Neuroregeneration Research Institute, Harvard Medical School/McLean Hospital, Belmont, MA 02478</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Smith, Gaynor A" sort="Smith, Gaynor A" uniqKey="Smith G" first="Gaynor A" last="Smith">Gaynor A. Smith</name><affiliation wicri:level="2"><nlm:affiliation>Neuroregeneration Research Institute, Harvard Medical School/McLean Hospital, Belmont, MA 02478, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Neuroregeneration Research Institute, Harvard Medical School/McLean Hospital, Belmont, MA 02478</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Park, Eric" sort="Park, Eric" uniqKey="Park E" first="Eric" last="Park">Eric Park</name><affiliation wicri:level="2"><nlm:affiliation>Shire, 300 Shire Way, Lexington, MA 02421, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Shire, 300 Shire Way, Lexington, MA 02421</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Cao, Hongmei" sort="Cao, Hongmei" uniqKey="Cao H" first="Hongmei" last="Cao">Hongmei Cao</name><affiliation wicri:level="2"><nlm:affiliation>Shire, 300 Shire Way, Lexington, MA 02421, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Shire, 300 Shire Way, Lexington, MA 02421</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Brown, Eilish" sort="Brown, Eilish" uniqKey="Brown E" first="Eilish" last="Brown">Eilish Brown</name><affiliation wicri:level="2"><nlm:affiliation>Shire, 300 Shire Way, Lexington, MA 02421, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Shire, 300 Shire Way, Lexington, MA 02421</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Hayes, Melissa A" sort="Hayes, Melissa A" uniqKey="Hayes M" first="Melissa A" last="Hayes">Melissa A. Hayes</name><affiliation wicri:level="2"><nlm:affiliation>Neuroregeneration Research Institute, Harvard Medical School/McLean Hospital, Belmont, MA 02478, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Neuroregeneration Research Institute, Harvard Medical School/McLean Hospital, Belmont, MA 02478</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Beagan, Jonathan" sort="Beagan, Jonathan" uniqKey="Beagan J" first="Jonathan" last="Beagan">Jonathan Beagan</name><affiliation wicri:level="2"><nlm:affiliation>Neuroregeneration Research Institute, Harvard Medical School/McLean Hospital, Belmont, MA 02478, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Neuroregeneration Research Institute, Harvard Medical School/McLean Hospital, Belmont, MA 02478</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Mclean, Jesse R" sort="Mclean, Jesse R" uniqKey="Mclean J" first="Jesse R" last="Mclean">Jesse R. Mclean</name><affiliation wicri:level="2"><nlm:affiliation>Neuroregeneration Research Institute, Harvard Medical School/McLean Hospital, Belmont, MA 02478, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Neuroregeneration Research Institute, Harvard Medical School/McLean Hospital, Belmont, MA 02478</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Izen, Sarah C" sort="Izen, Sarah C" uniqKey="Izen S" first="Sarah C" last="Izen">Sarah C. Izen</name><affiliation wicri:level="2"><nlm:affiliation>Neuroregeneration Research Institute, Harvard Medical School/McLean Hospital, Belmont, MA 02478, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Neuroregeneration Research Institute, Harvard Medical School/McLean Hospital, Belmont, MA 02478</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Perez Torres, Eduardo" sort="Perez Torres, Eduardo" uniqKey="Perez Torres E" first="Eduardo" last="Perez-Torres">Eduardo Perez-Torres</name><affiliation wicri:level="2"><nlm:affiliation>Neuroregeneration Research Institute, Harvard Medical School/McLean Hospital, Belmont, MA 02478, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Neuroregeneration Research Institute, Harvard Medical School/McLean Hospital, Belmont, MA 02478</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Hallett, Penelope J" sort="Hallett, Penelope J" uniqKey="Hallett P" first="Penelope J" last="Hallett">Penelope J. Hallett</name><affiliation wicri:level="2"><nlm:affiliation>Neuroregeneration Research Institute, Harvard Medical School/McLean Hospital, Belmont, MA 02478, USA. Electronic address: phallett@mclean.harvard.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Neuroregeneration Research Institute, Harvard Medical School/McLean Hospital, Belmont, MA 02478</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Isacson, Ole" sort="Isacson, Ole" uniqKey="Isacson O" first="Ole" last="Isacson">Ole Isacson</name><affiliation wicri:level="2"><nlm:affiliation>Neuroregeneration Research Institute, Harvard Medical School/McLean Hospital, Belmont, MA 02478, USA. Electronic address: isacson@hms.harvard.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Neuroregeneration Research Institute, Harvard Medical School/McLean Hospital, Belmont, MA 02478</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2015">2015</date><idno type="RBID">pubmed:26392287</idno><idno type="pmid">26392287</idno><idno type="doi">10.1016/j.nbd.2015.09.009</idno><idno type="wicri:Area/PubMed/Corpus">000404</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000404</idno><idno type="wicri:Area/PubMed/Curation">000404</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000404</idno><idno type="wicri:Area/PubMed/Checkpoint">000404</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000404</idno><idno type="wicri:Area/Ncbi/Merge">001D21</idno><idno type="wicri:Area/Ncbi/Curation">001D21</idno><idno type="wicri:Area/Ncbi/Checkpoint">001D21</idno><idno type="wicri:Area/Main/Merge">000710</idno><idno type="wicri:Area/Main/Curation">000709</idno><idno type="wicri:Area/Main/Exploration">000709</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Glucocerebrosidase gene therapy prevents α-synucleinopathy of midbrain dopamine neurons.</title><author><name sortKey="Rocha, Emily M" sort="Rocha, Emily M" uniqKey="Rocha E" first="Emily M" last="Rocha">Emily M. Rocha</name><affiliation wicri:level="2"><nlm:affiliation>Neuroregeneration Research Institute, Harvard Medical School/McLean Hospital, Belmont, MA 02478, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Neuroregeneration Research Institute, Harvard Medical School/McLean Hospital, Belmont, MA 02478</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Smith, Gaynor A" sort="Smith, Gaynor A" uniqKey="Smith G" first="Gaynor A" last="Smith">Gaynor A. Smith</name><affiliation wicri:level="2"><nlm:affiliation>Neuroregeneration Research Institute, Harvard Medical School/McLean Hospital, Belmont, MA 02478, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Neuroregeneration Research Institute, Harvard Medical School/McLean Hospital, Belmont, MA 02478</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Park, Eric" sort="Park, Eric" uniqKey="Park E" first="Eric" last="Park">Eric Park</name><affiliation wicri:level="2"><nlm:affiliation>Shire, 300 Shire Way, Lexington, MA 02421, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Shire, 300 Shire Way, Lexington, MA 02421</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Cao, Hongmei" sort="Cao, Hongmei" uniqKey="Cao H" first="Hongmei" last="Cao">Hongmei Cao</name><affiliation wicri:level="2"><nlm:affiliation>Shire, 300 Shire Way, Lexington, MA 02421, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Shire, 300 Shire Way, Lexington, MA 02421</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Brown, Eilish" sort="Brown, Eilish" uniqKey="Brown E" first="Eilish" last="Brown">Eilish Brown</name><affiliation wicri:level="2"><nlm:affiliation>Shire, 300 Shire Way, Lexington, MA 02421, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Shire, 300 Shire Way, Lexington, MA 02421</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Hayes, Melissa A" sort="Hayes, Melissa A" uniqKey="Hayes M" first="Melissa A" last="Hayes">Melissa A. Hayes</name><affiliation wicri:level="2"><nlm:affiliation>Neuroregeneration Research Institute, Harvard Medical School/McLean Hospital, Belmont, MA 02478, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Neuroregeneration Research Institute, Harvard Medical School/McLean Hospital, Belmont, MA 02478</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Beagan, Jonathan" sort="Beagan, Jonathan" uniqKey="Beagan J" first="Jonathan" last="Beagan">Jonathan Beagan</name><affiliation wicri:level="2"><nlm:affiliation>Neuroregeneration Research Institute, Harvard Medical School/McLean Hospital, Belmont, MA 02478, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Neuroregeneration Research Institute, Harvard Medical School/McLean Hospital, Belmont, MA 02478</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Mclean, Jesse R" sort="Mclean, Jesse R" uniqKey="Mclean J" first="Jesse R" last="Mclean">Jesse R. Mclean</name><affiliation wicri:level="2"><nlm:affiliation>Neuroregeneration Research Institute, Harvard Medical School/McLean Hospital, Belmont, MA 02478, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Neuroregeneration Research Institute, Harvard Medical School/McLean Hospital, Belmont, MA 02478</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Izen, Sarah C" sort="Izen, Sarah C" uniqKey="Izen S" first="Sarah C" last="Izen">Sarah C. Izen</name><affiliation wicri:level="2"><nlm:affiliation>Neuroregeneration Research Institute, Harvard Medical School/McLean Hospital, Belmont, MA 02478, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Neuroregeneration Research Institute, Harvard Medical School/McLean Hospital, Belmont, MA 02478</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Perez Torres, Eduardo" sort="Perez Torres, Eduardo" uniqKey="Perez Torres E" first="Eduardo" last="Perez-Torres">Eduardo Perez-Torres</name><affiliation wicri:level="2"><nlm:affiliation>Neuroregeneration Research Institute, Harvard Medical School/McLean Hospital, Belmont, MA 02478, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Neuroregeneration Research Institute, Harvard Medical School/McLean Hospital, Belmont, MA 02478</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Hallett, Penelope J" sort="Hallett, Penelope J" uniqKey="Hallett P" first="Penelope J" last="Hallett">Penelope J. Hallett</name><affiliation wicri:level="2"><nlm:affiliation>Neuroregeneration Research Institute, Harvard Medical School/McLean Hospital, Belmont, MA 02478, USA. Electronic address: phallett@mclean.harvard.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Neuroregeneration Research Institute, Harvard Medical School/McLean Hospital, Belmont, MA 02478</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Isacson, Ole" sort="Isacson, Ole" uniqKey="Isacson O" first="Ole" last="Isacson">Ole Isacson</name><affiliation wicri:level="2"><nlm:affiliation>Neuroregeneration Research Institute, Harvard Medical School/McLean Hospital, Belmont, MA 02478, USA. Electronic address: isacson@hms.harvard.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Neuroregeneration Research Institute, Harvard Medical School/McLean Hospital, Belmont, MA 02478</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author></analytic><series><title level="j">Neurobiology of disease</title><idno type="eISSN">1095-953X</idno><imprint><date when="2015" type="published">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Dependovirus (genetics)</term><term>Disease Models, Animal</term><term>Dopamine (metabolism)</term><term>Dopaminergic Neurons (enzymology)</term><term>Dopaminergic Neurons (pathology)</term><term>Female</term><term>Genetic Therapy (methods)</term><term>Genetic Vectors</term><term>Glucosylceramidase (genetics)</term><term>Glucosylceramidase (metabolism)</term><term>Humans</term><term>Male</term><term>Mesencephalon (enzymology)</term><term>Mesencephalon (pathology)</term><term>Mice, Transgenic</term><term>Neurodegenerative Diseases (enzymology)</term><term>Neurodegenerative Diseases (pathology)</term><term>Neurodegenerative Diseases (therapy)</term><term>Rats, Sprague-Dawley</term><term>alpha-Synuclein (genetics)</term><term>alpha-Synuclein (metabolism)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Glucosylceramidase</term><term>alpha-Synuclein</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Dopamine</term><term>Glucosylceramidase</term><term>alpha-Synuclein</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Dopaminergic Neurons</term><term>Mesencephalon</term><term>Neurodegenerative Diseases</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Dependovirus</term></keywords><keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Genetic Therapy</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Dopaminergic Neurons</term><term>Mesencephalon</term><term>Neurodegenerative Diseases</term></keywords><keywords scheme="MESH" qualifier="therapy" xml:lang="en"><term>Neurodegenerative Diseases</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Disease Models, Animal</term><term>Female</term><term>Genetic Vectors</term><term>Humans</term><term>Male</term><term>Mice, Transgenic</term><term>Rats, Sprague-Dawley</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Diminished lysosomal function can lead to abnormal cellular accumulation of specific proteins, including α-synuclein, contributing to disease pathogenesis of vulnerable neurons in Parkinson's disease (PD) and related α-synucleinopathies. GBA1 encodes for the lysosomal hydrolase glucocerebrosidase (GCase), and mutations in GBA1 are a prominent genetic risk factor for PD. Previous studies showed that in sporadic PD, and in normal aging, GCase brain activity is reduced and levels of corresponding glycolipid substrates are increased. The present study tested whether increasing GCase through AAV-GBA1 intra-cerebral gene delivery in two PD rodent models would reduce the accumulation of α-synuclein and protect midbrain dopamine neurons from α-synuclein-mediated neuronal damage. In the first model, transgenic mice overexpressing wildtype α-synuclein throughout the brain (ASO mice) were used, and in the second model, a rat model of selective dopamine neuron degeneration was induced by AAV-A53T mutant α-synuclein. In ASO mice, intra-cerebral AAV-GBA1 injections into several brain regions increased GCase activity and reduced the accumulation of α-synuclein in the substantia nigra and striatum. In rats, co-injection of AAV-GBA1 with AAV-A53T α-synuclein into the substantia nigra prevented α-synuclein-mediated degeneration of nigrostriatal dopamine neurons by 6 months. These neuroprotective effects were associated with altered protein expression of markers of autophagy. These experiments demonstrate, for the first time, the neuroprotective effects of increasing GCase against dopaminergic neuron degeneration, and support the development of therapeutics targeting GCase or other lysosomal genes to improve neuronal handling of α-synuclein.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Massachusetts</li></region></list><tree><country name="États-Unis"><region name="Massachusetts"><name sortKey="Rocha, Emily M" sort="Rocha, Emily M" uniqKey="Rocha E" first="Emily M" last="Rocha">Emily M. Rocha</name></region><name sortKey="Beagan, Jonathan" sort="Beagan, Jonathan" uniqKey="Beagan J" first="Jonathan" last="Beagan">Jonathan Beagan</name><name sortKey="Brown, Eilish" sort="Brown, Eilish" uniqKey="Brown E" first="Eilish" last="Brown">Eilish Brown</name><name sortKey="Cao, Hongmei" sort="Cao, Hongmei" uniqKey="Cao H" first="Hongmei" last="Cao">Hongmei Cao</name><name sortKey="Hallett, Penelope J" sort="Hallett, Penelope J" uniqKey="Hallett P" first="Penelope J" last="Hallett">Penelope J. Hallett</name><name sortKey="Hayes, Melissa A" sort="Hayes, Melissa A" uniqKey="Hayes M" first="Melissa A" last="Hayes">Melissa A. Hayes</name><name sortKey="Isacson, Ole" sort="Isacson, Ole" uniqKey="Isacson O" first="Ole" last="Isacson">Ole Isacson</name><name sortKey="Izen, Sarah C" sort="Izen, Sarah C" uniqKey="Izen S" first="Sarah C" last="Izen">Sarah C. Izen</name><name sortKey="Mclean, Jesse R" sort="Mclean, Jesse R" uniqKey="Mclean J" first="Jesse R" last="Mclean">Jesse R. Mclean</name><name sortKey="Park, Eric" sort="Park, Eric" uniqKey="Park E" first="Eric" last="Park">Eric Park</name><name sortKey="Perez Torres, Eduardo" sort="Perez Torres, Eduardo" uniqKey="Perez Torres E" first="Eduardo" last="Perez-Torres">Eduardo Perez-Torres</name><name sortKey="Smith, Gaynor A" sort="Smith, Gaynor A" uniqKey="Smith G" first="Gaynor A" last="Smith">Gaynor A. Smith</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Canada/explor/ParkinsonCanadaV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000709 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000709 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Canada
|area= ParkinsonCanadaV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= pubmed:26392287
|texte= Glucocerebrosidase gene therapy prevents α-synucleinopathy of midbrain dopamine neurons.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:26392287" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a ParkinsonCanadaV1
| This area was generated with Dilib version V0.6.29. |  |