Overexpression of human α-synuclein causes dopamine neuron death in rat primary culture and immortalized mesencephalon-derived cells
Identifieur interne : 001B93 ( Main/Exploration ); précédent : 001B92; suivant : 001B94Overexpression of human α-synuclein causes dopamine neuron death in rat primary culture and immortalized mesencephalon-derived cells
Auteurs : Wenbo Zhou [États-Unis] ; Marc S. Hurlbert [États-Unis] ; Jerome Schaack [États-Unis] ; Kedar N. Prasad [États-Unis] ; Curt R. Freed [États-Unis]Source :
- Brain Research [ 0006-8993 ] ; 2000.
English descriptors
- KwdEn :
Abstract
Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the appearance of intracytoplasmic inclusions called Lewy bodies (LB) in dopamine neurons in the substantia nigra and the progressive loss of these neurons. Recently, mutations in the α-synuclein gene have been identified in early-onset familial PD, and α-synuclein has been shown to be a major component of LB in all patients. Yet, the pathophysiological function of α-synuclein remains unknown. In this report, we have investigated the toxic effects of adenovirus-mediated α-synuclein overexpression on dopamine neurons in rat primary mesencephalic cultures and in a rat dopaminergic cell line – the large T-antigen immortalized, mesencephalon-derived 1RB3AN27 (N27). Adenovirus-transduced cultures showed high-level expression of α-synuclein within the cells. Overexpression of human mutant α-synuclein (Ala53Thr) selectively induced apoptotic programmed cell death of primary dopamine neurons as well as N27 cells. The mutant protein also potentiated the neurotoxicity of 6-hydroxydopamine (6-OHDA). By contrast, overexpression of wild-type human α-synuclein was not directly neurotoxic but did increase cell death after 6-OHDA. Overexpression of wild-type rat α-synuclein had no effect on dopamine cell survival or 6-OHDA neurotoxicity. These results indicate that overexpression of human mutant α-synuclein directly leads to dopamine neuron death, and overexpression of either human mutant or human wild-type α-synuclein renders dopamine neurons more vulnerable to neurotoxic insults.
Url:
DOI: 10.1016/S0006-8993(00)02215-0
Affiliations:
Links toward previous steps (curation, corpus...)
Le document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Overexpression of human α-synuclein causes dopamine neuron death in rat primary culture and immortalized mesencephalon-derived cells</title><author><name sortKey="Zhou, Wenbo" sort="Zhou, Wenbo" uniqKey="Zhou W" first="Wenbo" last="Zhou">Wenbo Zhou</name></author><author><name sortKey="Hurlbert, Marc S" sort="Hurlbert, Marc S" uniqKey="Hurlbert M" first="Marc S." last="Hurlbert">Marc S. Hurlbert</name></author><author><name sortKey="Schaack, Jerome" sort="Schaack, Jerome" uniqKey="Schaack J" first="Jerome" last="Schaack">Jerome Schaack</name></author><author><name sortKey="Prasad, Kedar N" sort="Prasad, Kedar N" uniqKey="Prasad K" first="Kedar N." last="Prasad">Kedar N. Prasad</name></author><author><name sortKey="Freed, Curt R" sort="Freed, Curt R" uniqKey="Freed C" first="Curt R." last="Freed">Curt R. Freed</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:4C5CE643F1677A0D2A520C202DA78CA5818B5711</idno><date when="2000" year="2000">2000</date><idno type="doi">10.1016/S0006-8993(00)02215-0</idno><idno type="url">https://api.istex.fr/document/4C5CE643F1677A0D2A520C202DA78CA5818B5711/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">002413</idno><idno type="wicri:Area/Main/Curation">002087</idno><idno type="wicri:Area/Main/Exploration">001B93</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Overexpression of human α-synuclein causes dopamine neuron death in rat primary culture and immortalized mesencephalon-derived cells</title><author><name sortKey="Zhou, Wenbo" sort="Zhou, Wenbo" uniqKey="Zhou W" first="Wenbo" last="Zhou">Wenbo Zhou</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Clinical Pharmacology C-237, Departments of Medicine and Pharmacology, and the Neuroscience Program, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, CO 80262</wicri:regionArea><placeName><region type="state">Colorado</region></placeName></affiliation></author><author><name sortKey="Hurlbert, Marc S" sort="Hurlbert, Marc S" uniqKey="Hurlbert M" first="Marc S." last="Hurlbert">Marc S. Hurlbert</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Clinical Pharmacology C-237, Departments of Medicine and Pharmacology, and the Neuroscience Program, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, CO 80262</wicri:regionArea><placeName><region type="state">Colorado</region></placeName></affiliation></author><author><name sortKey="Schaack, Jerome" sort="Schaack, Jerome" uniqKey="Schaack J" first="Jerome" last="Schaack">Jerome Schaack</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, CO 80262</wicri:regionArea><placeName><region type="state">Colorado</region></placeName></affiliation></author><author><name sortKey="Prasad, Kedar N" sort="Prasad, Kedar N" uniqKey="Prasad K" first="Kedar N." last="Prasad">Kedar N. Prasad</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Vitamins and Cancer Research, Department of Radiology, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, CO 80262</wicri:regionArea><placeName><region type="state">Colorado</region></placeName></affiliation></author><author><name sortKey="Freed, Curt R" sort="Freed, Curt R" uniqKey="Freed C" first="Curt R." last="Freed">Curt R. Freed</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Clinical Pharmacology C-237, Departments of Medicine and Pharmacology, and the Neuroscience Program, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, CO 80262</wicri:regionArea><placeName><region type="state">Colorado</region></placeName></affiliation><affiliation><wicri:noCountry code="no comma">Corresponding author. Tel.: +1-303-315-8455; fax: +1-303-315-3272</wicri:noCountry></affiliation><affiliation wicri:level="1"><country wicri:rule="url">États-Unis</country></affiliation></author></analytic><monogr></monogr><series><title level="j">Brain Research</title><title level="j" type="abbrev">BRES</title><idno type="ISSN">0006-8993</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="2000">2000</date><biblScope unit="volume">866</biblScope><biblScope unit="issue">1–2</biblScope><biblScope unit="page" from="33">33</biblScope><biblScope unit="page" to="43">43</biblScope></imprint><idno type="ISSN">0006-8993</idno></series><idno type="istex">4C5CE643F1677A0D2A520C202DA78CA5818B5711</idno><idno type="DOI">10.1016/S0006-8993(00)02215-0</idno><idno type="PII">S0006-8993(00)02215-0</idno><idno type="ArticleID">16482</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0006-8993</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>6-Hydroxydopamine</term><term>Adenovirus</term><term>Disorders of the nervous system</term><term>Dopamine neuron</term><term>Neurotoxicity</term><term>Parkinson’s disease</term><term>α-Synuclein</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the appearance of intracytoplasmic inclusions called Lewy bodies (LB) in dopamine neurons in the substantia nigra and the progressive loss of these neurons. Recently, mutations in the α-synuclein gene have been identified in early-onset familial PD, and α-synuclein has been shown to be a major component of LB in all patients. Yet, the pathophysiological function of α-synuclein remains unknown. In this report, we have investigated the toxic effects of adenovirus-mediated α-synuclein overexpression on dopamine neurons in rat primary mesencephalic cultures and in a rat dopaminergic cell line – the large T-antigen immortalized, mesencephalon-derived 1RB3AN27 (N27). Adenovirus-transduced cultures showed high-level expression of α-synuclein within the cells. Overexpression of human mutant α-synuclein (Ala53Thr) selectively induced apoptotic programmed cell death of primary dopamine neurons as well as N27 cells. The mutant protein also potentiated the neurotoxicity of 6-hydroxydopamine (6-OHDA). By contrast, overexpression of wild-type human α-synuclein was not directly neurotoxic but did increase cell death after 6-OHDA. Overexpression of wild-type rat α-synuclein had no effect on dopamine cell survival or 6-OHDA neurotoxicity. These results indicate that overexpression of human mutant α-synuclein directly leads to dopamine neuron death, and overexpression of either human mutant or human wild-type α-synuclein renders dopamine neurons more vulnerable to neurotoxic insults.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Colorado</li></region></list><tree><country name="États-Unis"><region name="Colorado"><name sortKey="Zhou, Wenbo" sort="Zhou, Wenbo" uniqKey="Zhou W" first="Wenbo" last="Zhou">Wenbo Zhou</name></region><name sortKey="Freed, Curt R" sort="Freed, Curt R" uniqKey="Freed C" first="Curt R." last="Freed">Curt R. Freed</name><name sortKey="Freed, Curt R" sort="Freed, Curt R" uniqKey="Freed C" first="Curt R." last="Freed">Curt R. Freed</name><name sortKey="Hurlbert, Marc S" sort="Hurlbert, Marc S" uniqKey="Hurlbert M" first="Marc S." last="Hurlbert">Marc S. Hurlbert</name><name sortKey="Prasad, Kedar N" sort="Prasad, Kedar N" uniqKey="Prasad K" first="Kedar N." last="Prasad">Kedar N. Prasad</name><name sortKey="Schaack, Jerome" sort="Schaack, Jerome" uniqKey="Schaack J" first="Jerome" last="Schaack">Jerome Schaack</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/ParkinsonV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001B93 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 001B93 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Sante
|area= ParkinsonV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= ISTEX:4C5CE643F1677A0D2A520C202DA78CA5818B5711
|texte= Overexpression of human α-synuclein causes dopamine neuron death in rat primary culture and immortalized mesencephalon-derived cells
}}
| This area was generated with Dilib version V0.6.23. |  |