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Identification of distinct physiochemical properties of the toxic prefibrillar species formed by Aβ peptide variants
Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär Bioteknik. Linköpings universitet, Tekniska högskolan.
Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär Bioteknik. Linköpings universitet, Tekniska högskolan.
Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.ORCID-id: 0000-0002-5582-140X
Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Experimentell patologi.
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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. Vol. 420, nr 4, s. 895-900
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Identifikatorer
URN: urn:nbn:se:liu:diva-73185DOI: 10.1016/j.bbrc.2012.03.097ISI: 000303619100034OAI: oai:DiVA.org:liu-73185DiVA, id: diva2:468477
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
Inngår i avhandling
1. The Alzheimer Aβ Peptide: Identification of Properties Distinctive for Toxic Prefibrillar Species
Åpne denne publikasjonen i ny fane eller vindu >>The Alzheimer Aβ Peptide: Identification of Properties Distinctive for Toxic Prefibrillar Species
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:nbn:se:liu:diva-76741 (URN)LIU-TEK-LIC-2012:11 (Lokal ID)978-91-7519-930-6 (ISBN)LIU-TEK-LIC-2012:11 (Arkivnummer)LIU-TEK-LIC-2012:11 (OAI)
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: 2012-12-04bibliografisk kontrollert

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