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dc.contributor.author
Alza, Natalia Paola  
dc.contributor.author
Salvador, Gabriela Alejandra  
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  
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  
dc.subject.classification
Ciencias Biológicas  
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS  
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  
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  
dc.conicet.rol
Autor  
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  
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  
dc.date.eventoHasta
2020-11-05  
dc.type
Congreso