umu.sePublikationer
Ändra sökning
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Effects of small-molecule amyloid modulators on a Drosophila model of Parkinson's disease
Visa övriga samt affilieringar
2017 (Engelska)Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, nr 9, artikel-id e0184117Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Alpha-synuclein (aS) amyloid formation is involved in Parkinson's disease (PD); therefore, small molecules that target aS and affect its aggregation are of interest as future drug candidates. We recently reported modified ring-fused 2-pyridones that modulate aS amyloid formation in vitro. Here, we describe the effects of such molecules on behavioral parameters of a Drosophila model of PD (i.e., flies expressing human aS), using a new approach (implemented in a commercially available FlyTracker system) to quantify fly mobility. FlyTracker allows for automated analysis of walking and climbing locomotor behavior, as it collects large sequences of data over time in an unbiased manner. We found that the molecules per se have no toxic or kinetic effects on normal flies. Feeding aS-expressing flies with the amyloid-promoting molecule FN075, remarkably, resulted in increased fly mobility at early time points; however, this effect switched to reduced mobility at later time points, and flies had shorter life spans than controls. In contrast, an amyloid inhibitor increased both fly kinetics and life span. In agreement with increased aS amyloid formation, the FN075-fed flies had less soluble aS, and in vitro aS-FN075 interactions stimulated aS amyloid formation. In addition to a new quantitative approach to probe mobility (available in FlyTracker), our results imply that aS regulates brain activity such that initial removal (here, by FN075-triggered assembly of aS) allows for increased fly mobility.

Ort, förlag, år, upplaga, sidor
2017. Vol. 12, nr 9, artikel-id e0184117
Nationell ämneskategori
Farmaceutiska vetenskaper
Identifikatorer
URN: urn:nbn:se:umu:diva-139797DOI: 10.1371/journal.pone.0184117ISI: 000408816900026PubMedID: 28863169OAI: oai:DiVA.org:umu-139797DiVA, id: diva2:1145002
Tillgänglig från: 2017-09-27 Skapad: 2017-09-27 Senast uppdaterad: 2018-06-09Bibliografiskt granskad

Open Access i DiVA

fulltext(4852 kB)82 nedladdningar
Filinformation
Filnamn FULLTEXT01.pdfFilstorlek 4852 kBChecksumma SHA-512
21caebf36e13b2f5324a0fa01362f1a79f4bae02540826a48fe982576e4aa7ec1224ffebf23c5ee4e892b91fef050840a83015aeddef1ebe92aaabe14a5b9d02
Typ fulltextMimetyp application/pdf

Övriga länkar

Förlagets fulltextPubMed

Personposter BETA

Chorell, ErikAlmqvist, Fredrik

Sök vidare i DiVA

Av författaren/redaktören
Chorell, ErikAlmqvist, Fredrik
Av organisationen
Kemiska institutionen
I samma tidskrift
PLoS ONE
Farmaceutiska vetenskaper

Sök vidare utanför DiVA

GoogleGoogle Scholar
Totalt: 82 nedladdningar
Antalet nedladdningar är summan av nedladdningar för alla fulltexter. Det kan inkludera t.ex tidigare versioner som nu inte längre är tillgängliga.

doi
pubmed
urn-nbn

Altmetricpoäng

doi
pubmed
urn-nbn
Totalt: 647 träffar
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf