RT info:eu-repo/semantics/article
T1 Dopamine transporter glycosylation correlates with the vulnerability of midbrain dopaminergic cells in Parkinson's disease
A1 Castro Hernández, Javier
A1 Afonso Oramas, Domingo
A1 de la Cruz Muros, Ignacio
A1 Álvarez de la Rosa, Diego
A1 Abreu González, Pedro
A1 Giráldez, Teresa
A1 Salas Hernández, Josmar
A1 Lanciego, José L.
A1 Rodríguez, Manuel
A1 González Hernández, Tomás
A2 Medicina Física y Farmacología
A2 Vulnerabilidad y plasticidad neuronal
K1 Parkinson's disease
K1 Pathogenesis
K1 Dopamine transporter
K1 Glycosylation
K1 Differential vulnerability
AB The dopamine transporter (DAT) is a membrane glycoprotein responsible for dopamine (DA) uptake, whichhas been involved in the degeneration of DA cells in Parkinson's disease (PD). Given that DAT activitydepends on its glycosylation status and membrane expression, and that not all midbrain DA cells show thesame susceptibility to degeneration in PD, we have investigated a possible relationship between DATglycosylation and function and the differential vulnerability of DA cells. Glycosylated DAT expression, DAuptake, and DAT Vmax were significantly higher in terminals of nigrostriatal neurons than in those ofmesolimbic neurons. No differences were found in non-glycosylated DAT expression and DAT Km, and DAuptake differences disappeared after deglycosylation of nigrostriatal synaptosomes. The expression patternof glycosylated DAT in the human midbrain and striatum showed a close anatomical relationship with DAdegeneration in parkinsonian patients. This relationship was confirmed in rodent and monkey models of PD,and in HEK cells expressing the wild-type and a partially deglycosylated DAT form. These results stronglysuggest that DAT glycosylation is involved in the differential vulnerability of midbrain DA cells in PD.
YR 2009
FD 2009
LK http://riull.ull.es/xmlui/handle/915/34770
UL http://riull.ull.es/xmlui/handle/915/34770
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DS Repositorio institucional de la Universidad de La Laguna
RD 14-ene-2025