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Changes in secondar...
Changes in secondary structure of alpha-synuclein during oligomerization induced by reactive aldehydes
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- Cai, Yixiao (författare)
- Uppsala universitet,Tillämpad materialvetenskap
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- Lendel, Christofer (författare)
- KTH,Tillämpad fysikalisk kemi
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- Österlund, Lars, 1967- (författare)
- Uppsala universitet,Fasta tillståndets fysik
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Kasrayan, Alex (författare)
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- Lannfelt, Lars (författare)
- Uppsala universitet,Geriatrik
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- Ingelsson, Martin (författare)
- Uppsala universitet,Geriatrik
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- Nikolajeff, Fredrik (författare)
- Uppsala universitet,Tillämpad materialvetenskap
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- Karlsson, Mikael (författare)
- Uppsala universitet,Tillämpad materialvetenskap
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- Bergström, Joakim (författare)
- Uppsala universitet,Geriatrik
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(creator_code:org_t)
- Elsevier BV, 2015
- 2015
- Engelska.
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Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 464:1, s. 336-341
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- The oxidative stress-related reactive aldehydes 4-hydroxy-2-nonenal (HNE) and 4-oxo-2-nonenal (ONE) have been shown to promote formation of alpha-synuclein oligomers in vitro. However, the changes in secondary structure of alpha-synuclein and the kinetics of the oligomerization process are not known and were the focus of this study. Size exclusion chromatography showed that after 1 h of incubation, HNE induced the formation of an oligomeric alpha-synuclein peak with a molecular weight of about similar to 2000 kDa, which coincided with a decreasing similar to 50 kDa monomeric peak. With prolonged incubation (up to 24 h) the oligomeric peak became the dominating molecular species. In contrast, in the presence of ONE, a similar to 2000 oligomeric peak was exclusively observed after 15 min of incubation and this peak remained constant with prolonged incubation. Western blot analysis of HNE-induced alpha-synuclein oligomers showed the presence of monomers (15 kDa), SDS-resistant low molecular (30-160 kDa) and high molecular weight oligomers (>= 260 kDa), indicating that the oligomers consisted of both covalent and non-covalent protein. In contrast, ONE-induced alpha-synuclein oligomers only migrated as covalent cross-linked high molecular-weight material (>= 300 kDa). Both circular dichroism (CD) and Attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy showed that the formation of HNE- and ONE-induced oligomers coincided with a spectral change from random coil to beta-sheet. However, ONE-induced alpha-synuclein oligomers exhibited a slightly higher degree of beta-sheet. Taken together, our results indicate that both HNE and ONE induce a change from random coil to beta-sheet structure that coincides with the formation of alpha-synuclein oligomers; albeit through different kinetic pathways depending on the degree of cross-linking. (C) 2015 Elsevier Inc. All rights reserved.
Ämnesord
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biofysik (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biophysics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
Nyckelord
- Alpha-synuclein
- Oligomers
- Aggregation
- Amyloid
- Oxidative stress
- 4-Hydroxy-2-nonenal
- 4-Oxo-2-nonenal
- Parkinson's disease
- Dementia with Lewy bodies
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Cai, Yixiao
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Lendel, Christof ...
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Österlund, Lars, ...
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Kasrayan, Alex
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Lannfelt, Lars
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Ingelsson, Marti ...
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Nikolajeff, Fred ...
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Karlsson, Mikael
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Bergström, Joaki ...
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- NATURVETENSKAP
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NATURVETENSKAP
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och Biologi
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- NATURVETENSKAP
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NATURVETENSKAP
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och Biofysik
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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Biochemical and ...
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Kungliga Tekniska Högskolan
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Uppsala universitet