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Interplay between A...
Interplay between APP and glypican-1 processing and α-synuclein aggregation in undifferentiated and differentiated human neural progenitor cells
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- Cheng, Fang (författare)
- Lund University,Lunds universitet,Glykobiologigruppen,Forskargrupper vid Lunds universitet,Glycobiology,Lund University Research Groups
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- Fransson, Lars Åke (författare)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Glykobiologigruppen,Forskargrupper vid Lunds universitet,Department of Experimental Medical Science,Faculty of Medicine,Glycobiology,Lund University Research Groups
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- Mani, Katrin (författare)
- Lund University,Lunds universitet,Glykobiologigruppen,Forskargrupper vid Lunds universitet,Glycobiology,Lund University Research Groups
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(creator_code:org_t)
- 2023-02-15
- 2023
- Engelska 17 s.
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Ingår i: Glycobiology. - : Oxford University Press (OUP). - 0959-6658 .- 1460-2423. ; 33:4, s. 325-341
- Relaterad länk:
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http://dx.doi.org/10... (free)
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Abstract
Ämnesord
Stäng
- In Parkinson’s disease, there is an accumulation of α-synuclein (SYN) aggregates in neurons, which is promoted by neuroinflammation. In neural cells, cytokine-induced SYN aggregation is modulated by heparan sulfate (HS) derived from glypican-1 (GPC1) by amyloid precursor protein (APP) and nitric oxide (NO)-dependent cleavage. We have explored possible interplay between APP, GPC1, and SYN in undifferentiated and differentiated neural progenitor cells (NPCs) by modulating APP and GPC1 processing. Effects were monitored by immunofluorescence microscopy and slot immunoblotting using antibodies recognizing APP degradation products, HS released from GPC1, and SYN aggregates (filamentous SYN [SYNfil]). Suppression of HS release from GPC1 by inhibition of β-secretase or by NO deprivation resulted in no or slight increase in SYNfil aggregation. Stimulation of HS release by ascorbate did not further increase SYNfil staining. Interleukin-6 (IL-6) induced increased APP and GPC1 processing and SYNfil formation, which was reduced when βsecretase was inhibited and when HS release was impeded by NO deprivation. Ascorbate restored APP and GPC1 processing but did not affect SYNfil formation. Ascorbate-dependent differentiation of NPC resulted in the expression of tyrosine hydroxylase (TH) which colocalized with SYNfil. Suppression of APP processing by inhibition of β-secretase greatly disturbed the differentiation process. IL-6 induced coclustering of APP-degradation products, TH, HS, and SYNfil, which could be reversed by stimulation of HS release from GPC1 by excess ascorbate. We suggest that continuous release of HS from GPC1 moderates SYN aggregation and supports differentiation of NPC to dopaminergic neurons.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Nyckelord
- amyloid precursor protein
- glypican-1
- heparan sulfate
- Parkinson’s disease
- α-synuclein
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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