liu.seSearch for publications in DiVA
Endre søk
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
The Alzheimer Aβ Peptide: Identification of Properties Distinctive for Toxic Prefibrillar Species
Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär Bioteknik. Linköpings universitet, Tekniska högskolan.
2012 (engelsk)Licentiatavhandling, med artikler (Annet vitenskapelig)
Abstract [en]

Proteins must have specific conformations to function correctly inside cells. However, sometimes they adopt the wrong conformation, causing dysfunction and disease. A number of amyloid diseases are caused by misfolded proteins that form amyloid fibrils. One such disease is Alzheimer’s disease (AD). The protein involved in this deadly disease is the amyloid β (Aβ) peptide. The formation of soluble prefibrillar oligomeric Aβ species has been recognized as an important factor in the development of AD. The aim of work described in this thesis was to investigate which properties of these oligomeric species can be linked to toxicity. We approached this task by comparing the aggregation behavior and biophysical properties of aggregates formed by variants of the Aβ peptide that have been shown to differ in neurotoxicity when expressed in the central nervous system (CNS) of Drosophila melanogaster. A combined set involving different fluorescent probes was used in parallell with transmission electron microscopy. The toxicity of species formed during the aggregation process was examined by exposing human SH-SY5Y neuroblastoma cells to Aβ aggregates. We deduced that there is a correlation between cell toxicity and the propensity of the Aβ peptide to form small prefibrillar assemblies at an early stage of aggregation in vitro. Moreover, these prefibrillar species were characterized by their ability to be recognized by pentamer formyl thiophene acetic acid (p-FTAA) and the presence of exposed hydrophobic patches. We also found that larger aggregates did not induce cell death.

sted, utgiver, år, opplag, sider
Linköping: Linköping University Electronic Press, 2012. , s. 44
Serie
Linköping Studies in Science and Technology. Thesis, ISSN 0280-7971 ; 1526
HSV kategori
Identifikatorer
URN: urn:nbn:se:liu:diva-76741Lokal ID: LIU-TEK-LIC-2012:11ISBN: 978-91-7519-930-6 (tryckt)OAI: oai:DiVA.org:liu-76741DiVA, id: diva2:516577
Presentation
2012-04-20, Planck, Fysikhuset, Campus Valla, Linköpings universitet, Linköping, 10:15 (engelsk)
Opponent
Tilgjengelig fra: 2012-04-18 Laget: 2012-04-18 Sist oppdatert: 2019-12-19bibliografisk kontrollert
Delarbeid
1. Identification of distinct physiochemical properties of the toxic prefibrillar species formed by Aβ peptide variants
Åpne denne publikasjonen i ny fane eller vindu >>Identification of distinct physiochemical properties of the toxic prefibrillar species formed by Aβ peptide variants
Vise andre…
2012 (engelsk)Inngår i: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 420, nr 4, s. 895-900Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

The formation of amyloid-β peptide (Aβ) aggregates at an early stage during the self-assembly process is an important factor in the development of Alzheimer’s disease. The toxic effect is believed to be exerted by prefibrillar species of Aβ. It is therefore important to identify which prefibrillar species are toxic and characterize their distinct properties. In the present study, we investigated the in vitro aggregation behavior of Aβ-derived peptides possessing different levels of neurotoxic activity, using fluorescence spectroscopy in combination with transmission electron microscopy. The toxicity of various Aβ aggregates was assessed by using cultures of human neuroblastoma cells. Through combined use of the fluorescence probe 8-anilino-1-napthalenesulfonate (ANS) and the novel luminescent probe pentamer formyl thiophene acetic acid (p-FTAA), we were able to identify those Aβ peptide-derived prefibrillar species which exhibited cellular toxicity. In particular, species, which formed early during the aggregation process and showed strong p-FTAA and ANS fluorescence, were the species that possessed toxic activities. Moreover, by manipulating the aggregation conditions, it was possible to change the capacity of the Aβ peptide to form nontoxic versus toxic species.

sted, utgiver, år, opplag, sider
Wiley-Blackwell, 2012
HSV kategori
Identifikatorer
urn:nbn:se:liu:diva-73185 (URN)10.1016/j.bbrc.2012.03.097 (DOI)000303619100034 ()
Merknad

funding agencies|Swedish National Graduate School in Science, Technology and Mathematics Education Research (Fon-tD)||Swedish Alzheimers Foundation||Soderberg foundation||

Tilgjengelig fra: 2011-12-21 Laget: 2011-12-21 Sist oppdatert: 2017-12-08bibliografisk kontrollert
2. Dissecting the Aggregation Events of Alzheimer’s disease Associated Aβ peptide Variants by the Combined use of Different Fluorescent Probes
Åpne denne publikasjonen i ny fane eller vindu >>Dissecting the Aggregation Events of Alzheimer’s disease Associated Aβ peptide Variants by the Combined use of Different Fluorescent Probes
Vise andre…
(engelsk)Manuskript (preprint) (Annet vitenskapelig)
Abstract [en]

The formation of soluble prefibrillar oligomeric species of the amyloid β peptide (Aβ) has been implicated as a causative agent in the development of Alzheimer’s disease (AD). It is therefore important to characterize the properties of these aggregates, which precede the formation of amyloid fibrils. We studied the in vitro aggregation process of two Aβ40 peptide variants through the combined use of four different fluorescent probes and transmission electron microscopy. Previous studies have shown that these two studied Aβ40 variants exhibit different levels of neurodegeneration when expressed in the central nervous system of Drosophila melanogaster. In the present study, we demonstrate distinct differences in aggregate morphology and their binding properties to different fluorescent probes during in vitro fibrillation of these Aβ peptides. Our results indicate a potential link between the observed neurodegenerative properties and the biophysical properties of distinct aggregated Aβ species.

HSV kategori
Identifikatorer
urn:nbn:se:liu:diva-76739 (URN)
Tilgjengelig fra: 2012-04-18 Laget: 2012-04-18 Sist oppdatert: 2014-04-08

Open Access i DiVA

The Alzheimer Aβ Peptide: Identification of Properties Distinctive for Toxic Prefibrillar Species(3370 kB)382 nedlastinger
Filinformasjon
Fil FULLTEXT01.pdfFilstørrelse 3370 kBChecksum SHA-512
fa064a91afc5e48172a6986be870999abdafceb68043e64808fd1f67d4a73d6327fe406c3e7c0e15b2fd5123f74bebe9feba0ff64811c917760f5ac785d24374
Type fulltextMimetype application/pdf
omslag(356 kB)62 nedlastinger
Filinformasjon
Fil COVER01.pdfFilstørrelse 356 kBChecksum SHA-512
908077bdfcae9bc6b514e7b8bbc44602c86d11d412186c01f6938f7b7fb796b8ffb86a6af3524ee78e64f4559e1bc6ad8aa6d75746c8626d7aff02e5dbe18fd2
Type coverMimetype application/pdf
Bestill online >>

Personposter BETA

Göransson, Anna-Lena

Søk i DiVA

Av forfatter/redaktør
Göransson, Anna-Lena
Av organisasjonen

Søk utenfor DiVA

GoogleGoogle Scholar
Totalt: 382 nedlastinger
Antall nedlastinger er summen av alle nedlastinger av alle fulltekster. Det kan for eksempel være tidligere versjoner som er ikke lenger tilgjengelige

isbn
urn-nbn

Altmetric

isbn
urn-nbn
Totalt: 179 treff
RefereraExporteraLink to record
Permanent link

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