Harnessing the trophic and modulatory potential of statins in a dopaminergic cell line.
Identifieur interne : 000271 ( Main/Exploration ); précédent : 000270; suivant : 000272Harnessing the trophic and modulatory potential of statins in a dopaminergic cell line.
Auteurs : Mathieu Schmitt [Belgique] ; Benjamin Dehay [France] ; Erwan Bezard [France] ; F Javier Garcia-Ladona [Belgique]Source :
- Synapse (New York, N.Y.) [ 1098-2396 ] ; 2016.
English descriptors
- KwdEn :
- Active Transport, Cell Nucleus (drug effects), Active Transport, Cell Nucleus (physiology), Adrenergic Uptake Inhibitors (pharmacology), Cell Enlargement (drug effects), Cell Line, Tumor, Dopamine (metabolism), Dopaminergic Neurons (cytology), Dopaminergic Neurons (drug effects), Dopaminergic Neurons (physiology), Dose-Response Relationship, Drug, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors (pharmacology), Lovastatin (pharmacology), Membrane Glycoproteins (metabolism), Nerve Tissue Proteins (metabolism), Neurites (drug effects), Neurites (physiology), RNA, Messenger (metabolism), Reserpine (pharmacology), Sterol Regulatory Element Binding Protein 1 (metabolism), Synaptogyrins (metabolism), Tetrabenazine (pharmacology), Vesicular Monoamine Transport Proteins (genetics), Vesicular Monoamine Transport Proteins (metabolism).
- MESH :
- chemical , genetics : Vesicular Monoamine Transport Proteins.
- chemical , metabolism : Dopamine, Membrane Glycoproteins, Nerve Tissue Proteins, RNA, Messenger, Sterol Regulatory Element Binding Protein 1, Synaptogyrins, Vesicular Monoamine Transport Proteins.
- chemical , pharmacology : Adrenergic Uptake Inhibitors, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Lovastatin, Reserpine, Tetrabenazine.
- cytology : Dopaminergic Neurons.
- drug effects : Active Transport, Cell Nucleus, Cell Enlargement, Dopaminergic Neurons, Neurites.
- physiology : Active Transport, Cell Nucleus, Dopaminergic Neurons, Neurites.
- Cell Line, Tumor, Dose-Response Relationship, Drug, Humans.
Abstract
The identification of an effective disease-modifying treatment for the neurodegenerative progression in Parkinson's disease (PD) remains a major challenge. Epidemiological studies have reported that intake of statins, cholesterol lowering drugs, could be associated to a reduced risk of developing PD. In-vivo studies suggest that statins may reduce the severity of dopaminergic neurodegeneration. The trophic potential of statins and their impact on the expression of dopaminergic synaptic markers and dopamine (DA) transport function in SH-SY5Y cells has been investigated. The findings showed that statin treatment induces neurite outgrowth involving a specific effect on the complexity of the neurite branching pattern. Statins increased the levels of presynaptic dopaminergic biomarkers such as vesicular monoamine transporter 2 (VMAT2), synaptic vesicle glycoproteins 2A and 2C (SV2C), and synaptogyrin-3 (SYNGR3). Gene expression analysis confirmed a rapid statin-induced up-regulation of VMAT2-, SV2C-, and SYNGR3-mRNA levels. Assessment of [(3) H]DA transport in statin-treated cells showed a reduction in DA uptake concomitant to a modification of VMAT2 pharmacological properties. It was also observed that a nuclear translocation of the sterol regulatory element-binding protein 1 (SREBP-1). The results suggested that statins induced phenotypic changes in dopaminergic cells characterized by an increase of growth, complexity of structural synaptic elements, and expression of key presynaptic proteins with functional impact on the DA transport capacity. Statin-induced changes are likely the result of a downstream modulation of SREBP-1 pathway. Overall, these mechanisms may contribute to the neuroprotective or neurorestorative effects observed in the dopaminergic system and strengthen the therapeutic potential of statins for PD.
Url:
DOI: 10.1002/syn.21881
PubMed: 26695835
Affiliations:
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Benjamin" sort="Dehay, Benjamin" uniqKey="Dehay B" first="Benjamin" last="Dehay">Benjamin Dehay</name><affiliation wicri:level="3"><nlm:affiliation>University De Bordeaux, Institut Des Maladies Neurodégénératives, UMR 5293, Bordeaux, 33000, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>University De Bordeaux, Institut Des Maladies Neurodégénératives, UMR 5293, Bordeaux, 33000</wicri:regionArea><placeName><region type="region" nuts="2">Nouvelle-Aquitaine</region><region type="old region" nuts="2">Aquitaine</region></placeName></affiliation></author><author><name sortKey="Bezard, Erwan" sort="Bezard, Erwan" uniqKey="Bezard E" first="Erwan" last="Bezard">Erwan Bezard</name><affiliation wicri:level="3"><nlm:affiliation>University De Bordeaux, Institut Des Maladies Neurodégénératives, UMR 5293, Bordeaux, 33000, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>University De Bordeaux, Institut Des Maladies 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Inhibitors</term><term>Lovastatin</term><term>Reserpine</term><term>Tetrabenazine</term></keywords><keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>Dopaminergic Neurons</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Active Transport, Cell Nucleus</term><term>Cell Enlargement</term><term>Dopaminergic Neurons</term><term>Neurites</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Active Transport, Cell Nucleus</term><term>Dopaminergic Neurons</term><term>Neurites</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Cell Line, Tumor</term><term>Dose-Response Relationship, Drug</term><term>Humans</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The identification of an effective disease-modifying treatment for the neurodegenerative progression in Parkinson's disease (PD) remains a major challenge. Epidemiological studies have reported that intake of statins, cholesterol lowering drugs, could be associated to a reduced risk of developing PD. In-vivo studies suggest that statins may reduce the severity of dopaminergic neurodegeneration. The trophic potential of statins and their impact on the expression of dopaminergic synaptic markers and dopamine (DA) transport function in SH-SY5Y cells has been investigated. The findings showed that statin treatment induces neurite outgrowth involving a specific effect on the complexity of the neurite branching pattern. Statins increased the levels of presynaptic dopaminergic biomarkers such as vesicular monoamine transporter 2 (VMAT2), synaptic vesicle glycoproteins 2A and 2C (SV2C), and synaptogyrin-3 (SYNGR3). Gene expression analysis confirmed a rapid statin-induced up-regulation of VMAT2-, SV2C-, and SYNGR3-mRNA levels. Assessment of [(3) H]DA transport in statin-treated cells showed a reduction in DA uptake concomitant to a modification of VMAT2 pharmacological properties. It was also observed that a nuclear translocation of the sterol regulatory element-binding protein 1 (SREBP-1). The results suggested that statins induced phenotypic changes in dopaminergic cells characterized by an increase of growth, complexity of structural synaptic elements, and expression of key presynaptic proteins with functional impact on the DA transport capacity. Statin-induced changes are likely the result of a downstream modulation of SREBP-1 pathway. Overall, these mechanisms may contribute to the neuroprotective or neurorestorative effects observed in the dopaminergic system and strengthen the therapeutic potential of statins for PD.</div></front></TEI><affiliations><list><country><li>Belgique</li><li>France</li></country><region><li>Aquitaine</li><li>Nouvelle-Aquitaine</li><li>Vienne (Autriche)</li></region><settlement><li>Vienne (Autriche)</li></settlement></list><tree><country name="Belgique"><region name="Vienne (Autriche)"><name sortKey="Schmitt, Mathieu" sort="Schmitt, Mathieu" uniqKey="Schmitt M" first="Mathieu" last="Schmitt">Mathieu Schmitt</name></region><name sortKey="Garcia Ladona, F Javier" sort="Garcia Ladona, F Javier" uniqKey="Garcia Ladona F" first="F Javier" last="Garcia-Ladona">F Javier Garcia-Ladona</name></country><country name="France"><region name="Nouvelle-Aquitaine"><name sortKey="Dehay, Benjamin" sort="Dehay, Benjamin" uniqKey="Dehay B" first="Benjamin" last="Dehay">Benjamin Dehay</name></region><name sortKey="Bezard, Erwan" sort="Bezard, Erwan" uniqKey="Bezard E" first="Erwan" last="Bezard">Erwan Bezard</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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