Brain endothelial p-glycoprotein level is reduced in parkinson’s disease via a vitamin d receptor-dependent pathway
DC Field | Value | Language |
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dc.contributor.author | Kim, H. | - |
dc.contributor.author | Shin, J.-Y. | - |
dc.contributor.author | Lee, Y.-S. | - |
dc.contributor.author | Yun, S.P. | - |
dc.contributor.author | Maeng, H.-J. | - |
dc.contributor.author | Lee, Y. | - |
dc.date.available | 2020-12-16T01:40:42Z | - |
dc.date.created | 2020-11-23 | - |
dc.date.issued | 2020-11 | - |
dc.identifier.issn | 1661-6596 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/79354 | - |
dc.description.abstract | The progressive neurodegeneration in Parkinson’s disease (PD) is accompanied by neuroinflammation and endothelial vascular impairment. Although the vitamin D receptor (VDR) is expressed in both dopamine neurons and brain endothelial cells, its role in the regulation of endothelial biology has not been explored in the context of PD. In a 6-hydroxydopamine (6-OHDA)-induced PD mouse model, we observed reduced transcription of the VDR and its downstream target genes, CYP24 and MDR1a. The 6-OHDA-induced transcriptional repression of these genes were recovered after the VDR ligand—1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) treatment. Similarly, reduced vascular protein expression of P-glycoprotein (P-gp), encoded by MDR1a, after 6-OHDA administration was reversed by 1,25(OH)2D3. Moreover, marked reduction of endothelial P-gp expression with concomitant α-synuclein aggregation was found in a combinatorial AAV-αSyn/αSyn preformed fibril (PFF) injection mouse model and postmortem PD brains. Supporting the direct effect of α-synuclein aggregation on endothelial biology, PFF treatment of human umbilical vein endothelial cells (HUVECs) was sufficient to induce α-synuclein aggregation and repress transcription of the VDR. PFF-induced P-gp downregulation and impaired functional activity in HUVECs completely recovered after 1,25(OH)2D3 treatment. Taken together, our results suggest that a dysfunctional VDR-P-gp pathway could be a potential target for the maintenance of vascular homeostasis in PD pathological conditions. © 2020 by the authors. Licensee MDPI, Basel, Switzerland. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | MDPI AG | - |
dc.relation.isPartOf | International Journal of Molecular Sciences | - |
dc.title | Brain endothelial p-glycoprotein level is reduced in parkinson’s disease via a vitamin d receptor-dependent pathway | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000594315800001 | - |
dc.identifier.doi | 10.3390/ijms21228538 | - |
dc.identifier.bibliographicCitation | International Journal of Molecular Sciences, v.21, no.22, pp.1 - 15 | - |
dc.description.isOpenAccess | N | - |
dc.identifier.scopusid | 2-s2.0-85096059134 | - |
dc.citation.endPage | 15 | - |
dc.citation.startPage | 1 | - |
dc.citation.title | International Journal of Molecular Sciences | - |
dc.citation.volume | 21 | - |
dc.citation.number | 22 | - |
dc.contributor.affiliatedAuthor | Maeng, H.-J. | - |
dc.type.docType | Article | - |
dc.subject.keywordAuthor | 6-hydroxydopamine | - |
dc.subject.keywordAuthor | Brain endothelium | - |
dc.subject.keywordAuthor | P-glycoprotein | - |
dc.subject.keywordAuthor | Parkinson’s disease | - |
dc.subject.keywordAuthor | Vitamin D receptor | - |
dc.subject.keywordAuthor | α-synuclein aggregation | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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