TY  - JOUR
AU  - Letoha, Tamás
AU  - Hudák, Anett
AU  - Kusz, Erzsébet
AU  - Pettkó-Szandtner, Aladár
AU  - Racskóné Domonkos, Ildikó
AU  - Jósvay, Katalin
AU  - Hofmann-Apitius, Martin
AU  - Szilák, László
TI  - Contribution of syndecans to cellular internalization and fibrillation of amyloid-β (1–42)
JF  - SCIENTIFIC REPORTS
J2  - SCI REP
VL  - 9
PY  - 2019
IS  - 1
PG  - 17
SN  - 2045-2322
DO  - 10.1038/s41598-018-37476-9
UR  - https://m2.mtmt.hu/api/publication/30462206
ID  - 30462206
N1  - Pharmacoidea Ltd., Szeged, H-6726, Hungary            
            Biological Research Centre of the Hungarian Academy of Sciences, Szeged, H-6726, Hungary            
            Fraunhofer Institute for Algorithms and Scientific Computing (SCAI), Sankt Augustin, 53754, Germany            
            Szilak Laboratories, Bioinformatics and Molecule-Design, Szeged, H-6723, Hungary            
            Cited By :3            
            Export Date: 18 February 2020            
            Correspondence Address: Letoha, T.; Pharmacoidea Ltd.Hungary; email: tamas.letoha@pharmacoidea.eu
Pharmacoidea Ltd., Szeged, H-6726, Hungary            
            Biological Research Centre of the Hungarian Academy of Sciences, Szeged, H-6726, Hungary            
            Fraunhofer Institute for Algorithms and Scientific Computing (SCAI), Sankt Augustin, 53754, Germany            
            Szilak Laboratories, Bioinformatics and Molecule-Design, Szeged, H-6723, Hungary            
            Cited By :3            
            Export Date: 20 February 2020            
            Correspondence Address: Letoha, T.; Pharmacoidea Ltd.Hungary; email: tamas.letoha@pharmacoidea.eu
AB  - Intraneuronal accumulation of amyloid-beta(1-42) (A beta 1-42) is one of the earliest signs of Alzheimer's disease (AD). Cell surface heparan sulfate proteoglycans (HSPGs) have profound influence on the cellular uptake of A beta 1-42 by mediating its attachment and subsequent internalization into the cells. Colocalization of amyloid plaques with members of the syndecan family of HSPGs, along with the increased expression of syndecan-3 and -4 have already been reported in postmortem AD brains. Considering the growing evidence on the involvement of syndecans in the pathogenesis of AD, we analyzed the contribution of syndecans to cellular uptake and fibrillation of A beta 1-42. Among syndecans, the neuron specific syndecan-3 isoform increased cellular uptake of A beta 1-42 the most. Kinetics of A beta 1-42 uptake also proved to be fairly different among SDC family members: syndecan-3 increased A beta 1-42 uptake from the earliest time points, while other syndecans facilitated A beta 1-42 internalization at a slower pace. Internalized A beta 1-42 colocalized with syndecans and flotillins, highlighting the role of lipid-rafts in syndecan-mediated uptake. Syndecan-3 and 4 also triggered fibrillation of A beta 1-42, further emphasizing the pathophysiological relevance of syndecans in plaque formation. Overall our data highlight syndecans, especially the neuron-specific syndecan-3 isoform, as important players in amyloid pathology and show that syndecans, regardless of cell type, facilitate key molecular events in neurodegeneration.
LA  - English
DB  - MTMT
ER  -