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dc.contributor.author
Alza, Natalia Paola
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dc.contributor.author
Salvador, Gabriela Alejandra
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dc.date.available
2023-02-08T19:44:57Z
dc.date.issued
2020
dc.identifier.citation
Intersections between alpha-synuclein and cholesterol: an unsolved case; LVI SAIB Meeting; XV SAMIGE Meeting 2020; Virtual; Argentina; 2020; 43-43
dc.identifier.issn
0327-9545
dc.identifier.uri
http://hdl.handle.net/11336/187402
dc.description.abstract
A pathological sign of synucleinopathies, including Parkinson's disease, is the aggregation and fibrillation of α-synuclein (αsyn), a small presynaptic protein characterized by a high lipid binding affinity. How α-syn and cholesterol are interconnected in the context of these neurodegenerative disorders remains an open question. In this work, we investigated cholesterol homeostasis in a neuronal model of α-syn overexpression (WT α-syn cells). We found that both free cholesterol and cholesteryl ester levels were increased by α-syn overexpression. The raise in cholesteryl esters was associated with an increased acylCoA:cholesterol acyltransferase activity. While cholesteryl esters were part of the lipid droplet core in WT α-syn cells, free cholesterol was located in membrane compartments and lysosomes. Co-staining experiments revealed that cholesterol was accumulated in lysosomes in cells overexpressing α-syn, though the distribution of these organelles and the expression of lysosomal markers, LAMP-1 and Lysotracker, were not altered. In order to determine the mechanism for the increased cholesterol levels, the status of the transcription factor sterol regulatory element-binding protein (SREBP)-2 was evaluated. SREBP-2 nuclear translocation was induced by α-syn overexpression, in agreement with the in silico analysis carried out through the MyProteinNet server (Yeger-Lotem lab). The latter showed a relationship between α-syn and sterol regulatory element-binding gen (SREBF-2). Paradoxically, the activation of SREBP-2 was not accompanied by the expected upregulation of involved canonical downstream genes in cholesterol synthesis, such as 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and 24-dehydrocholesterol reductase. Moreover, cholesterol content was not altered by the inhibition of HMGCR by mevastatin in WT α-syn cells, thus implying that cholesterolgenesis was not responsible for its increase. Our findings suggest that α-syn overexpression disrupts cholesterol trafficking resulting in the lysosomal sequestration and consequent ER transport impairment. Further studies should be performed to ascertain the mechanisms and functional implications of cholesterol uptake and intracellular trafficking alterations associated with synucleinopathies. Funding: ANPCyT, CONICET, and UNS.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Tech Science Press
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dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Alpha-synuclein
dc.subject
Cholesterol homeostasis
dc.subject
Synucleinopathies
dc.subject.classification
Bioquímica y Biología Molecular
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dc.subject.classification
Ciencias Biológicas
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dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
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dc.title
Intersections between alpha-synuclein and cholesterol: an unsolved case
dc.type
info:eu-repo/semantics/publishedVersion
dc.type
info:eu-repo/semantics/conferenceObject
dc.type
info:ar-repo/semantics/documento de conferencia
dc.date.updated
2023-02-01T14:55:10Z
dc.identifier.eissn
1667-5746
dc.journal.volume
45
dc.journal.number
suplemento 1
dc.journal.pagination
43-43
dc.journal.pais
Argentina
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dc.journal.ciudad
Mendoza
dc.description.fil
Fil: Alza, Natalia Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Química; Argentina
dc.description.fil
Fil: Salvador, Gabriela Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.techscience.com/biocell/v45nSuppl.1/42376
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://file.techscience.com/uploads/attached/file/20210427/20210427073650_26441.pdf
dc.conicet.rol
Autor
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dc.conicet.rol
Autor
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dc.coverage
Nacional
dc.type.subtype
Congreso
dc.description.nombreEvento
LVI SAIB Meeting; XV SAMIGE Meeting 2020
dc.date.evento
2020-11-02
dc.description.ciudadEvento
Virtual
dc.description.paisEvento
Argentina
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dc.type.publicacion
Journal
dc.description.institucionOrganizadora
Argentine Society for Biochemistry and Molecular Biology
dc.description.institucionOrganizadora
Argentinean Society for General Microbiology
dc.source.revista
Biocell
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dc.date.eventoHasta
2020-11-05
dc.type
Congreso
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